Manchester City defender Nathan Ake was injured only five minutes into the Netherlands’ 1-1 friendly draw with Spain in Amsterdam.
Ake, 25, has made six Premier League appearances for City since his mutli million pound move, but went off with a hamstring problem.
Sergio Canales put Spain ahead but Manchester United midfielder Donny van de Beek volleyed in an equaliser.
Both countries play two more Nations League games this week.
City manager Pep Guardiola, along with his Premier League counterparts at Liverpool and Manchester United, called for a change in scheduling and a return to five substitutions before this international break because of the impact on players.
Joe Gomez went down with an injury on Wednesday at training. Another Liverpool defender in their long list of injuries at the back.