After suffering their first Premier League defeat of the season in their away clash with Crystal Palace, Liverpool may have hoped for an easier follow-up game than a trip to the vociferous Rams Park for a tricky meeting with Galatasaray.
If they were in any doubt, the Reds were made fully aware in the opening few minutes that this would be a tough assignment, with Alisson forced to thwart Barış Yılmaz in a one-on-one situation.
Just over 10 minutes later, the Liverpool goalkeeper was facing up to a Osimhen penalty after Yılmaz went down under a challenge from makeshift right-back Dominik Szoboszlai - only seconds after Cody Gakpo had an effort clear off the line at the opposite end of the pitch.
Osimhen took no chances with his spot-kick, thumping it straight down the middle to score his sixth goal in as many matches against English opposition.
Florian Wirtz threatened to provide a swift response when he drew a diving stop from Uğurcan Çakır, but in truth, Liverpool could have little complaints about the HT scoreline following an error-strewn display in the first period.
Another moment of sloppiness after the restart saw Osimhen intercept a poor pass and race through to fire a shot at Alisson, who picked up a game-ending injury in the process of making the save.
As a result, Arne Slot had to summon Giorgi Mamardashvili for his first UCL appearance, not long before the Reds boss returned to his bench to introduce Alexander Isak, Conor Bradley and the talismanic Mohamed Salah in a bid to find a way back into the contest.
As Liverpool continued to struggle against Galatasaray’s determined backline, they looked set to receive a lifeline when referee Clément Turpin pointed to the spot in the closing stages, only for the decision against Wilfried Singo to be overturned following a VAR review.
The subsequent eight minutes of added time were not enough for Liverpool, who have now failed to win their last three away H2Hs and head into a trip to Chelsea at the weekend with questions to answer after a second successive defeat.
Flashscore Man of the Match: Victor Osimhen (Galatasaray)