Wales have suffered a double defensive blow ahead of their opening 2022 World Cup qualifier in Belgium.
Tottenham full-back Ben Davies and Luton centre-back Tom Lockyer have both been ruled out of Wednesday's Group E clash in Leuven, as well as upcoming matches against Mexico and the Czech Republic.
A Football Association of Wales statement said: "Ben Davies and Tom Lockyer have both withdrawn from the squad due to injury."
The loss of the 58-times capped Davies will be particularly felt by caretaker manager Robert Page as the Spurs player would have been a certain starter in the World Cup qualifiers in Belgium and at home to the Czech Republic on Tuesday.
Lockyer's absence is less surprising as the Hatters defender has not played since sustaining an ankle injury against Cardiff last month.
Davies might well have featured in a three-man central defence in Belgium and Page has few options in that area for the Leuven opener.
Wales also play a friendly against Mexico in Cardiff on Saturday, where Page is expected to field a side consisting mostly of fringe players.