After a hard-fought 2-2 draw with 1. FC Union Berlin at the weekend, Marvin Matip was ruled out for the remainder of their campaign with a broken humerus.
Matip scored the opening goal on Sunday, though a spectacular brace from Björn Jopek and Tobias Levels' equaliser ensured the game ended all square.
"This diagnosis is quite a shock to us," said Ingolstadt sporting director Thomas Linke. "Nevertheless, we have had to compensate for personal setbacks in the past and are confident that we will succeed this time."
The 29-year-old centre-back has been instrumental in their run to the top of the league, featuring in every game this season and scoring three goals so far. Kicker rank Matip as the best central defender and the second best player in the 2. Bundesliga, with only Pascal Groß ahead of him.
Experienced defender Andre Mijatovic is the obvious candidate to take over in the final four games. Ralph Hasenhüttel's men still have to face 1. FC Nürnberg, VfL Bochum, RB leipzig and a potential title-decider against 1. FC Kasierslautern on the final day.
Quotes via kicker.