Mayo's injury troubles have escalated ahead of next weekend's Connacht championship opener against London.
Ger Cafferkey and Enda Varley both sat out training last Sunday and while Varley's absence was described as precautionary, it looks like Cafferkey will not make the game after picking up a hamstring injury last week. Defender Keith Higgins (knee) and midfielder Ronan McGarrity (Achilles) are already ruled out.
Cafferkey lined out at full-back in Mayo's last challenge match against Offaly -- with Varley at corner-forward -- but he is also experienced at centre-back and gives manager James Horan options.
London have lost many of their better-known players of recent years, but manager Paul Coggins has also picked up some notable newcomers, including former Galway senior Mark Gottsche and Mike Maloney, who won an U-21 All-Ireland with Kerry in 2008.
Maloney, a noted full-back, lined out for Kerry in the McGrath Cup last January, while Gottsche played for the Tribesmen under Liam Sammon in 2008.
Elsewhere Tyrone's Joe McMahon could be back in action much sooner than anticipated. McMahon was expected to miss the entire Ulster championship after suffering a double jaw fracture in a club game, but manager Mickey Harte has revealed that he could be back as early as the provincial semi-final if Tyrone beat Monaghan in their first-round tie.
"The good news is that Joe is recovering and will be back at some stage of the season, whether that be in the Ulster semi-final or a qualifier game," he said.
Harte described McMahon's loss for Tyrone's opener as "as big as it gets".
"You look at some players, and they can play one or two positions, which is great, but you look at Joe McMahon and he can play in any position," Harte said. "To lose a player as versatile and capable as that is a huge loss. There's no telling the impact that will have on us as a team, but we'll have to live with that. It's very unfortunate."
Tyrone will also be without Enda McGinley on Sunday week as he needs a second operation on an ankle problem.