Seamus O'Shea is expected to be sidelined for a number of weeks after dislocating his shoulder in Mayo's win over Tipperary.
The Breaffy clubman was forced off just before half-time after landing awkwardly and received oxygen from medics as he left the pitch.
With Tom Parsons ruled out for the rest of the season after sustaining a serious leg injury in last month's Connacht SFC quarter-final loss to Galway, O'Shea's injury further reduces Mayo's midfield options.
"Shoulder injury, possible dislocation - probably a dislocation, actually," Mayo manager Stephen Rochford told RTÉ.
"It was unfortunate, but that probably goes back to an earlier point - not really a good pass, he went in for it and fell awkwardly on his shoulder. That definitely rules him out for the foreseeable future."
Mayo are no strangers to the All-Ireland SF qualifiers and Rochford was stressing the importance of getting the recovery right as they take their place in the bowl for tomorrow's Round 3 draw.
"That's what happens through the qualifiers. You're going to have games and moments that not just test your physical but mental resolve.
"We know the coaching, the strength and conditioning and all that, have the guys in really good shape. And they need to be, we are into another game in seven days after playing in that heat. Crucial for the next period," he added.