Arne Slot's side are out of this season's FA Cup after a 1-0 defeat by a penalty at Plymouth's Home Park.
The struggling Championship side equipped themselves well against a Liverpool team that had 10 changes from the side that sealed a return to Wembley with a comprehensive demolition of Spurs earlier in the week.
Joe Gomez, playing his first game back from injury, lasted 11 minutes and had to pass on the captain's armband.
Liverpool did start with Chiesa and Luis Diaz up front but neither were dominant.
Youngsters McConnell, Nyoni and (on for Gomez) Mabaya all featured in what was a relatively limited attacking performance.
It took for the second half for any real opportunities to present themselves and first up was Plymouth who converted a penalty in the 53rd minute - Harvey Elliott with the handball inside the area.
The reds did have chances as they saw the clock ticking down, but Conor Hazard pulled off some excellent saves that kept Plymouth in the tie and saw them through to the next round.
Slot clearly felt he had picked a team capable of winning, but as he has found out - there is a big difference between playing a League Two team at home and an arduous trek to the corner of the country to face a Championship side away from home.
Plymouth secured their first victory over the reds in over 65 years, and Liverpool must now concentrate on the three remaining competitions.
First on that list is the 'game in hand' - the final Merseyside derby at Goodison Park. Hopefully confidence will not be dented too much.
MOTM: Wataru Endo
MATCH HIGHLIGHTS: Plymouth 1-0 Liverpool
