Aston Villa kept their UEFA Conference League dream alive with a 2-1 quarter-final first leg win over Lille at Villa Park, but both Liverpool and West Ham United have their work cut out if they are to progress in the UEFA Europa League.
Ollie Watkins and John McGinn were the goal heroes at Villa Park, but former West Ham striker Gianluca Scamacca struck twice to help Italian side Atalanta end Liverpool's 33-match unbeaten run at Anfield with a stunning 3-0 win.
West Ham were hit by two goals in the last seven minutes as their European ambitions were dented in a 2-0 loss at Bayer Leverkusen.
Villa secure vital first-leg advantage
Unai Emery named the same team who drew 3-3 with Brentford on Saturday in his 1,000th match as a manager.
Former Tottenham Hotspur midfielder Nabil Bentaleb started for Lille, who also had ex-Manchester United midfielder Angel Gomes on the bench.
Emery's side got off to a great start after only 11 minutes when Watkins scored with a fine header from McGinn's corner. It was his 25th goal across all competitions in 2023/24 - the joint-most by a Villa player in a Premier League season alongside Dwight Yorke in 1995/96.
Watkins slammed a shot into the side-netting, but it was the turn of Villa goalkeeper Emiliano Martinez to take centre stage with three outstanding close-range saves to deny Lille in the first half.
Villa, yet to lose when scoring first at home this season, were in no mood to relinquish that proud record and doubled their lead after 57 minutes with a low finish by McGinn after Leon Bailey slipped the ball through to him from a Douglas Luiz corner.
Lille's Bafode Diakite pulled a goal back with a flicked header from Gomes's delivery with six minutes remaining to leave the tie finely posed.
Before then, Villa's focus will be firmly on Sunday, when they face a huge top-four contest at Premier League leaders Arsenal, before travelling to Lille for the second leg in France on Thursday 18 April.
Scamacca's double stuns Liverpool
There were six changes to the Liverpool side that drew at Manchester United, with Joe Gomez, Ibrahima Konate, Curtis Jones, Cody Gakpo, Harvey Elliott and Kostas Tsimikas replacing Conor Bradley, Jarell Quansah, Andrew Robertson, Dominik Szoboszlai, Mohamed Salah and Luis Diaz.
Diogo Jota and Trent Alexander-Arnold, who had both been sidelined since February, returned to the bench along with 19-year-old Spanish midfielder Stefan Bajcetic, who had also been out with injury.
Liverpool beaten by Atalanta in Europa League quarter-final first leg at Anfield
After a frenetic start, Liverpool created a great chance to go 1-0 up after 16 minutes, but Darwin Nunez pulled his effort well wide after Jones had played him through on goal.
That miss proved costly and Atalanta took full advantage, taking the lead after 38 minutes when Scamacca's first-time shot from a Davide Zappacosta cross trickled under the arms of goalkeeper Caoimhin Kelleher.
Liverpool have now kept just one clean sheet in their last 14 home matches in all competitions.
Kelleher made amends for his error, however, with a vital save from Teun Koopmeiners in a 1v1 moments before half time after Konate had lost possession.
Klopp sent on Szoboszlai, Salah and Robertson for the second half, but it was Atalanta who stunned the Anfield crowd with a second goal, and a second for Scamacca, placing a first-time shot past Kelleher from Charles De Ketelaere's superb cross.
It went from bad to worse for the Reds, who, having also brought on Jota, gifted possession to Atalanta in midfield, Ederson drew a save from Kelleher but the rebound fell straight to Mario Pasalic for a tap-in.
Liverpool will turn their attentions back to their title bid on Sunday when they host Crystal Palace, before making the trip to Italy for their quarter-final second leg on Thursday 18 April.
West Ham's hopes dealt double blow
David Moyes was forced to make two changes to West Ham's side from the XI that started their 2-1 win at Wolverhampton Wanderers last weekend. Jarrod Bowen was ruled out with a knee injury sustained at Molineux, while Edson Alvarez was suspended. Aaron Cresswell and Michail Antonio stepped in to the fold.
Leverkusen included former Arsenal star Granit Xhaka in a side that showed seven changes from Saturday's 1-0 Bundesliga victory at Union Berlin.
Late double puts Leverkusen in control of Europa League tie
Mohammed Kudus went close to putting West Ham ahead in the opening 10 minutes following a superb break from the halfway line by Antonio, but his effort was saved.
Xabi Alonso's Leverkusen began to get a foothold in the match, but West Ham defended stoically as they faced 18 first-half shots from their German opponents.
Lukasz Fabianski was in inspired form between the posts, with his save at full stretch from Edmond Tapsoba's 20-yarder the pick of the bunch in a goalless opening half.
Fabianski clawed away Patrik Schick's close-range header as Leverkusen kept the pressure on, before finally edging ahead through Jonas Hofmann's bobbling effort with seven minutes remaining.
Hofmann then turned provider, crossing for Victor Boniface to head home a second goal in the first minute of stoppage-time as Leverkusen extended their unbeaten run to 42 matches across all competitions.
West Ham return to Premier League action at home to London rivals Fulham on Sunday, before hosting Leverkusen - who could win their first ever Bundesliga title at the weekend - in the return leg on Thursday 18 April.
Both Lucas Paqueta and Emerson will, however, miss the London Stadium tie after being booked in the first leg.