Two St Mirren players have returned positive Covid-19 tests, while a further member of the first team squad is also self-isolating as a precaution.
The cases were detected in routine screening on Monday and were confirmed by subsequent NHS tests, and all three will miss Saturday’s Scottish Premiership meeting with Motherwell.
It is the second time this season the club have suffered an outbreak.
“Two of the three are big players,” said manager Jim Goodwin.
“It’s a blow to lose them and we’re low on numbers as it is. It’s one thing after another at the moment.”
In September, goalkeepers Jak Alnwick and Dean Lyness contracted the virus and third-choice Peter Urminsky missed a game as a precaution.
St Mirren had to sign Zdenek Zlamal on an emergency loan to cover their absences after having an attempt to have their game with Hibernian postponed turned down.
The players who are self-isolating this time – one of whom has been identified as a close contact of the two who have the illness – also face missing the visit of Hamilton Academical next weekend.
St Mirren have lost six league games in a row and manager Goodwin says the news was the last thing his squad needed.
“It’s very unsettling for the rest of the boys because you start to worry about your own situation,” he said. “It’s an anxious time for everybody but the players have dealt with it well so far.
“Footballers are not immune to this virus, no matter how hard we try. We are in a bubble at training but that bubble is burst as soon as we leave because we go home to parents, wives and kids.
“It’s frustrating but I worry that we’re not even into the worst of it yet, and that might come over the winter when the cough and cold season comes in.”
Meanwhile, Hamilton Academical head coach Brian Rice has revealed that defender Jamie Hamilton has tested positive for the virus, too.
Hamilton was part of the Scotland under-19 squad who had a game against England abandoned last week when coach Billy Stark was found to have the illness.