It's an uphill battle for Isak and Liverpool ahead of the return leg at Anfield next week.
When the Swedish national team striker was substituted with eleven minutes remaining, Liverpool were trailing 0-2.
It was Alexander Isak's first match since December 20, when he broke his fibula and injured his ankle against Tottenham in the Premier League.
For the national team, it is welcome news that Isak is back in action ahead of the World Cup finals in the USA, Mexico and Canada this summer.
Title holders Paris Saint-Germain dominated from the start and 20-year-old Désiré Doué scored 1-0 in the eleventh minute.
Doué's shot struck Liverpool's Ryan Gravenberch and ended up in the visitors' net off goalkeeper Giorgi Mamardashvili.
However, the Georgian goalkeeper kept a lacklustre Liverpool in the game with two great saves in the first half.
Liverpool stepped forward immediately after the break, but never really threatened.
Instead, PSG made it 2-0 after a neat solo run by Khvitja Kvarachelia, who fooled both the defense and his compatriot in goal, Mamardashvili.
PSG was 18-3 in the final and had two penalties coming - but both were waved off after VAR review.