McCarthy was the only Saints player or staff member to prove positive after the latest round of tests and is now in isolation.
The club posted on Twitter: “Ralph Hasenhuttl has confirmed Alex McCarthy will miss the Liverpool game following a positive Covid-19 test.
“McCarthy is currently self-isolating at home, in line with government guidelines and club protocols.”
Saints head coach Ralph Hasenhuttl is hoping to return to the dugout for the visit of the champions following a period of isolation after he recently tested positive.
Hasenhuttl missed his side’s goalless home draw against West Ham last Tuesday.
McCarthy, in his fifth season at St Mary’s after joining from Crystal Palace, has started in all 16 of their top-flight matches this season and has kept seven clean sheets.
Fraser Forster is likely to take his place on Monday.
The Saints were boosted for the West Ham match by the return to fitness of seven-goal striker Danny Ings, who came through unscathed after missing the previous goalless draw at Fulham due to a hamstring strain.
The striker had sustained an injury before Christmas, but with seven goals to his name already this season, Hasenhuttl believes Ings’ return to fitness is important for the club.
“I think he is OK, he had a good start in the game,” said Hasenhuttl before the news of McCarthy’s positive test.
“And yes it is normal after this injury that he is not 100 per cent (in his usual) rhythm, but it’s important that he stays fit now.
“He has enough time to recover now for the next game against his former club Liverpool.
“I am happy to have him back, and we must definitely have more punch up front to score goals in the future but this will happen, I am sure.”