Everton striker Andrew Johnson has pulled out of the England squad to face Spain in Wednesday's friendly because of an ankle injury.
The Toffees hitman had made a surprise return to action in Saturday's goalless Merseyside derby with Liverpool less than two weeks after being stretchered off against Wigan Athletic with a serious looking ankle injury.
However, the four-time England international has now pulled out of Steve McClaren's squad for the Old Trafford friendly.
Johnson doesn't feel his ankle problem has healed enough to play two games in the space of five days.
The absence of the former Crystal Palace star leaves McClaren with a potential striking headache as Wayne Rooney is also struggling with the ankle knock he picked up in Manchester United's victory over Tottenham.
Rooney was given permission by United to join up with his international colleagues despite being substituted in Sunday's rout at White Hart Lane.
The Football Association's medical staff will now asses Rooney's fitness before deciding whether to allow the Red Devils striker to take part in the match.
In the absence of Johnson and possibly Rooney, McClaren could hand starts to Liverpool's Peter Crouch and Jermain Defoe of Tottenham or opt to play a lone striker with Newcastle midfielder Kieron Dyer employed in a more advanced role.