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.
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