Italian Zanardi had left a Siena hospital on Tuesday to continue his recovery at a rehabilitation centre after undergoing three surgeries.
However, the 53-year-old has now been transferred to an intensive care unit due to “the instability of his clinical conditions”.
“Faced with the instability of the clinical conditions of the patient Alex Zanardi, it was decided to transfer him to the intensive therapy department of the San Raffaele hospital in Milan,” said a statement released by the hospital in Como where the rehab centre is based.
Officials said that no other information would be given for the moment.
Zanardi had both his legs amputated after a motor racing accident in 2001 at the Lausitzring track in Germany.
He has since become one of the best-known figures in Paralympic sports.
The Italian star suffered serious head injuries when he lost control of his handbike during a road race in Tuscany and crashed into an oncoming truck on June 19.
Zanardi raced for Jordan, Minardi and Lotus in F1 in the early 1990s before switching to the CART championship in the United States where he was series champion in 1997 and 1998.
He returned to F1 with Williams in 1999 before heading back to CART.
Zanardi won two gold medals at the 2012 London Paralympic Games and four years later won two more in Rio de Janeiro.
He also won the Rome marathon in 2010 and the New York race the following year.
Download our app and read this and other great stories on the move. Available for Android and iOS.