The pair started Sunday’s 1-0 defeat by Wales in Cardiff but have now been isolated from the rest of the group, which flew back to Dublin on Monday.
A Football Association of Ireland statement said: “The Football Association of Ireland can confirm Ireland defender Matt Doherty and forward James McClean have tested positive for Covid-19.
“The players have been isolated from the group as per Covid-19 protocols, and the HSE have been informed of this development.
“The rest of the staff and squad tested negative ahead of the flight back to Dublin this morning before the Uefa Nations League match against Bulgaria on Wednesday.”
The development represents a fresh headache for manager Stephen Kenny, who has already lost Callum Robinson and Alan Browne to positive tests this month.
With Seamus Coleman, Enda Stevens and John Egan missing through injury and James McCarthy having withdrawn from the squad for family reasons, Kenny’s resources were depleted further at the Cardiff City Stadium by Jeff Hendrick’s red card and the booking which will see fellow midfielder Jayson Molumby join him on the suspension list against Bulgaria.
Ireland need to avoid defeat at the Aviva Stadium to ensure they do not finish bottom of Group B4 and suffer relegation.