The 30-year-old picked up a flu before Saturday’s game with former club Borussia Monchengladbach, but played through the discomfort and even scored the only goal of the game in a 1-0 win.
Reus has however failed to win over the illness for a second time and manager Lucien Favre will be without his skipper when they travel to the San Siro on Wednesday.
Reus has made 12 appearances in all competitions this season, scoring six goals.
Dortmund will also be without the services of left back Marcel Schmelzer and striker Paco Alcacer, who are all serving time on the treatment table.
The absence of Reus and Alcacer will likely free up space for the inclusion of Jadon Sancho, who was suspended by the club for the weekend’s clash with Monchengladbach after making a late return from international duty.
Sancho, who has scored three goals and provided six assists this season, was fined €100,000 for his tardiness.
Dortmund are top of Group F on four points after two games but are level on points with second-placed Barcelona, while Inter Milan and Slavia Prague complete the standings with one point apiece.
Antonio Conte’s Inter Milan have made a bright start to the domestic season in Italy, sitting just a point behind champions Juventus after eight round of matches.
