Ruud van Nistelrooy will miss Holland's friendly match against Croatia.
The Real Madrid striker injured his right ankle during Saturday's 2-0 defeat to Almeria.
Holland coach Marco van Basten has yet to decide on whether to call up a replacement for the game at the Poljud Stadium in Split on 6th February.
Van Nistelrooy, who is currently top scorer for the La Liga leaders with 12 this season, is expected to return to action in 10 days.
A club statement read: "[Van Nistelrooy] will not be able to link up with the Dutch squad and will stay in Madrid to rest."
Milan's Clarence Seedorf and FC Twente's Orlando Engelaar have also been forced to withdraw after the duo both picked up ankle injuries.