Serie A leaders Napoli were knocked out of the Europa League on Thursday despite a 2-0 win at RB Leipzig, while Ciro Immobile's hat-trick sent Lazio into the last 16.
A 3-1 home defeat to the Bundesliga outfit last week left Napoli on the brink of elimination, goals from Piotr Zielinski and Lorenzo Insigne setting up a grandstand finish in the return fixture.
But it was not to be, Timo Werner's brace in the first leg proving enough to see RB Leipzig into the last 16 of the Europa League in what is the club's maiden European campaign.
There was better news for Napoli's Serie A rivals Lazio, though, as an Immobile treble - his third of the season - saw them emphatically overturn a first-leg deficit against Romanian side Steaua Bucharest.
First-leg loss leaves Napoli too much to do
Werner struck the second of his two goals at the Stadio San Paolo deep into added time and that effort from the Germany international proved the decisive moment.
Zielinski thumped in the rebound after Insigne's initial attempt was saved to give Napoli hope, but they could not find a second goal until the last five minutes.
Insigne got in front of his marker to nudge Napoli level on aggregate, but, despite intense pressure in the closing stages, RB Leipzig held firm to progress on away goals.
Immobile treble turns tie around for Lazio
Lazio had suffered a surprise 1-0 loss in the first leg in Romania, but the Serie A side came from behind to secure a comfortable 5-1 aggregate victory.
Ciro Immobile scored twice before half-time to reach 30 goals in all competitions for the season, with Bastos also on target as Simone Inzaghi's men routed Steaua 5-0 at the Stadio Olimpico.
Felipe Anderson struck after the interval to add to a comprehensive Lazio win, guaranteeing Serie A will be represented in Friday's last-16 draw, with Immobile wrapping up his hat-trick.
Denisov sends Lokomotiv through
Lokomotiv Moscow joined city rivals CSKA in the last 16 with a 1-0 win over Nice ensuring a 4-2 aggregate victory, Igor Denisov's well-taken finish deciding the encounter in the Russian capital.
A 3-1 win for Sporting CP in their first leg against Astana gave the Portuguese side a big advantage, which Bas Dost added to with an early header - his 10th aerial goal of the campaign.
Although Astana equalised, Bruno Fernandes struck a brace in a thrilling 3-3 draw that ensured Sporting went through with a 6-4 aggregate victory.
10 - Bas Dost scored his 10th headed goal for @Sporting_CP this season, having netted 26 goals this season in total. Giant.— OptaJohan (@OptaJohan) February 22, 2018
Lyon knock out 2015-16 semi-finalists
Spanish teams have a brilliant record in this competition, but 2015-16 semi-finalists Villarreal were knocked out by Lyon.
The Ligue 1 side led 3-1 after the first leg at home and when Jaume Costa was dismissed, Villarreal's hopes of a comeback were severely dashed - Bertrand Traore then on target to earn a 1-0 win and send Lyon through.
Elsewhere, goals from Michael Krmencik and Ales Cermak earned Viktoria Plzen a 2-0 win and 3-1 aggregate success against Partizan Belgrade, while Dynamo Kiev progressed on away goals after a 0-0 draw with AEK Athens.
|WATCH: Chargers top Chiefs on dramatic two-point conversion in final seconds|
|Suns owner Sarver committed to keeping team in Phoenix|
|Chargers WR Allen leaves with injury after near-spectacular catch|
|Socceroos not giving up on Mooy for Asian Cup|
|Cooper says Raiders owner wanted to trade him to Cowboys|
|Pochettino jokes Levy is ´worried´ about losing him|
|Barcelona would welcome Morata – Alba|
|Toure not a priority for West Ham – Pellegrini|
|Koscielny no certainty to face Southampton, says Emery|
|We gifted the game – AC Milan boss Gattuso furious after Europa League exit|
|My season starts now, says Koscielny|
|Cipriani ´at peace´ with latest England snub|
|Laporte: Deschamps must have personal reasons for France snub|
|Morata injury not too serious, claims Chelsea boss Sarri|
|Hansen to leave: All Blacks coach returning focus to World Cup defence|
|I want to fight the champion! - Joshua reiterates Wilder in April ambition|
|Gundogan glad to leave Christmas holidays behind|
|I know how it feels and it hurts - Gundogan on Sterling abuse|
|Celtic 1 Red Bull Salzburg 2: Scottish champions through despite defeat|
|Olympiacos 3 AC Milan 1: Rossoneri crash out of Europa League|
|Arsenal 1 Qarabag 0: Lacazette on target as Saka shines|
|Hansen to leave: All Blacks will take time to name replacement|
|Chelsea condemn alleged anti-Semitic chanting from fans|
|Hansen to leave: The best Opta facts from New Zealand coach´s tenure|
|Hansen to leave: Five contenders to be the next All Blacks coach|
|Hansen to leave: Highs and highs of his All Blacks reign|
|Hansen to leave All Blacks after World Cup|
|Rapid Vienna 1 Rangers 0: Late Ljubicic winner sends Gerrard´s men out|
|Beckham continues to miss Giants practice with quad injury|
|Vidi 2 Chelsea 2: Giroud spares Sarri´s side in lacklustre draw|
|Paris Saint-Germain and Marseille fixtures among latest Ligue 1 cancellations|
|Santos turn to ex-Argentina boss Sampaoli|
|Muller could miss Champions League last 16 after Tagliafico kick|
|Home hope Bekker out in front at Alfred Dunhill Championship|
|Van Bommel in touch with Robben over PSV reunion|
|Pinarello chief confident over Team Sky future|
|Stade make Ospreys tickets free in tribute to teenager|
|WRC great Loeb seals Hyundai switch|
|Madrid rumours better than sack talk, says Pochettino|
|Nadal to join Federer at 2019 Laver Cup|
|Prigoda smashes world record, Hosszu dethroned in Hangzhou|
|Former Juve CEO Marotta takes over at Inter|
|Glenn to stand down as FA boss next year|
|Muller apologises to Tagliafico for kick to the head|
|Pereira pleads for more Manchester United chances|
|Griffin hails ´phenomenal´ Lowry after Warriors demolition|
|I´ve played with Zidane and Henry, but Messi is something else – Pires|
|Dragons forward Jack de Belin charged with sexual assault|
|Durant: Raptors are the real deal|
|Cocu bids farewell to Fenerbahce after ´mutual agreement´ is made over October sacking|
|Australia unchanged for historic Perth Test|
|Champions League draw: The possible last-16 ties|
|Southee happy to be back on home soil|
|I wouldn´t swap Dembele for Neymar – Pires|
|Canelo ready to risk heavy weather against Fielding|
|Raptors upstage Warriors, Davis leads Pelicans with 44 points|
|India skipper Kohli excited by green Perth wicket|
|PSG? I haven´t decided my future yet – De Jong|
|Marcelo: Real Madrid don´t have attitude problem|
|India pair Ashwin, Rohit ruled out of second Test|
|Kovac: Ajax-Bayern draw was amazing|
|Sims re-signs with Dragons until 2022|
|Derrius Guice injury update: Redskins RB (knee) has rehab setback, undergoes 3 more procedures|
|Emery: Arsenal could sign defender in January|
|Phillies sign McCutchen to three-year deal|
|O´Neal thinks his Lakers teams could ´easily´ beat Warriors|
|A-League to add two clubs by 2020|
|Curry says he was ´obviously joking´ about moon landing comments|
|Now the beautiful part starts – Ronaldo ready for Champions League knockout stage|
|Bayern have a lot more potential – Lewandowski not satisfied despite top spot|