The centre back appeared to injure his ankle after a nasty challenge from an Ivory Coast player during the first half, with Dortmund and Germany's fears being confirmed when he was unable to come back out after half-time and was subbed off.
Early assessments of the knock do not look good either, with Germany head coach Julian Nagelsmann revealing the player would be going for an MRI to determine the extent of the damage.
"He has an issue with his medial ligament and needs to have an MRI tomorrow.. It's not looking too good - unfortunately," Nagelsmann said after the game.
Schlotterbeck felt the issue early on in the second half and tried to play through but ultimately had to withdraw during the break as the pain intensified.
"In the end, it is largely a tactical decision whether he can still perform. And he did very well until half-time," Nagelsmann revealed.
It is a big blow for Germany's World Cup plans after Schlotterbeck started both of their games at the tournament so far and they will now need to rethink their strategy at the back, with Antonio Rudiger the most likely player to stand in.
Germany showed a lot of grit and determination to win its Group E clash with Ivory Coast after falling behind and having two goals disallowed in the first half.
They bounced back well in the second period, scoring twice to earn a 2-1 win and a place in the knockout rounds of the competition.
"This was a win of the mentality, of the team spirit. We never gave up. We kept going and knew they would get tired," Jonathan Tah said after the game.
"The guys who came off the bench brought tremendous energy. Deniz has shown once again how important he is when he comes on.
"We knew it would be a tough game because Ivory Coast can play at a very high level. We have to keep going."