Brobbey went down in the 35th minute of the Germany clash with a hamstring injury, and although he was able to leave the pitch himself, he looked particularly uncomfortable.
The 24-year-old was seen limping heavily as he made his way down the tunnel, requiring assistance from Dutch backroom staff members in what is a huge worry for Sunderland at the start of the international break.
Brobbey has started all of Sunderland's five Premier League games so far, and the striker scored a hat-trick against Manchester City before the international break.
As Brobbey pulls out, United striker Zirkzee is set to take his place in the side, as confirmed by the KNVB on Friday morning.
Netherlands boss Xavi Hernández is putting his faith in Zirkzee, who has only played 74 minutes this season across just 4 appearances under United boss Michael Carrick.
Benjamin Šeško, Matheus Cunha, Bryan Mbeumo and Marcus Rashford all rank ahead of Zirkzee at United and the Netherlands may be worried about their chances against Serbia and Greece over the coming weeks.
Sunderland next face Brighton whilst United clash with Tottenham after the international break as Zirkzee aims to impress whilst away from Carrick's side, where he has little chance of any starts.