Sedov was a Moscow-based engineer who published works on thermodynamics and diesel engines. He became a professor at the Moscow Institute of Technology while still in his twenties.
Unlike his parents and his older brother Lev Sedov, Sergei Sedov was not active in politics. Nevertheless, he was caught up in the Great Purges as Trotsky's son. He was arrested in Moscow in early 1935 and sentenced to 5 years in exile in Krasnoyarsk, Siberia, in August 1935. After unsuccessfully searching for work in Krasnoyarsk (his letters to his wife from this period are in the Hoover Archives), he was re-arrested in 1936 and sent to a labor camp. More recently, Robert Service in Trotsky: A Biography, asserts that as an engineer Sergei did find work in a gold mine in Krasnoyarsk.
Sedov was killed in the next round of Stalin's purges in 1937, although the exact details of his death are unknown. The Soviet secret police, NKVD, announced in early 1937 that Sedov had been charged with trying to poison factory workers and the date of his final death sentence is believed to be October 29, 1937, but there have also been unconfirmed reports that he died in a prison uprising. His wife and her relatives were also arrested and spent years in exile and prisons.