Liverpool captain Virgil van Dijk and Barcelona midfielder Frenkie de Jong have withdrawn from the Netherlands squad ahead of Tuesday night's UEFA Nations League clash with Bosnia and Herzegovina.
Netherlands boss Ronald Koeman has confirmed both players have now returned to their respective clubs and will not feature in the final game this international break.
"For both it is better now to leave training camp," he said in a press release. "It's a decision based on medical grounds, putting the interest of the player at first."
Sources told ESPN Van Dijk's withdrawal is precautionary, with the 33-year-old not believed to be carrying an injury.
The Netherlands secured qualification for the Nations League quarterfinals with a 4-0 victory over Hungary on Saturday and therefore it is thought that Koeman has chosen not to take any unnecessary risks with two of his key players.
It was the first game back in the Netherlands national team in 13 months for De Jong, who last season battled with an ankle injury and missed out on the European Championship in Germany.
The Barcelona midfielder said he "still needs some time" before finding his form although his return to the Dutch side drew positive reviews.
Van Dijk has been close to an ever-present for Liverpool this season and played a key role in helping Arne Slot's side climb to the top of both the Premier League and Champions League tables.
Liverpool's next match is against Southampton at St Mary's Stadium on Nov. 24, before back-to-back clashes with Real Madrid and Manchester City.
Information from Reuters contributed to this report.