After Operation Barbarossa began, Mitrofanov was placed at the disposal of the commander-in-chief of the Northwestern Strategic Direction, and in September appointed chief of the Armored Forces of the 55th Army of the Leningrad Front. Appointed chief of staff of the 12th Tank Corps of the 3rd Tank Army of the Western Front in February 1942, he served as acting corps commander between 30 December and 16 January 1943. Mitrofanov participated in the Ostrogozhsk–Rossosh Offensive, Operation Star, and the Third Battle of Kharkov in early 1943.