Wehrlein crossed the finish line marginally behind opponent Felipe Massa at the exhibition event but then smashed through a barrier and made contact with Brazilian.
The German’s Polaris Slingshot SLR then flipped and hit a concrete wall but both driver and passenger somehow walked away from the incident seemingly unscathed.
However, doctors subsequently declared Wehrlein unfit to represent Germany alongside Ferrari F1 driver Sebastian Vettel on Sunday.
Pascal Wehrlein crashed at the Race of Champions after losing to Felipe Massa
Pascal Wehrlein's crash saw him turn the car over and clear several barriers
“I’d really like to race again and I feel fine, but the doctors have advised me to rest so of course I will take their advice,” Wehrlein said.
“It’s no more than mild discomfort but my real priority for the coming year is my Formula 1 season.
“So while I’m sad to be missing out on all the action, I send my best wishes to my team-mate Sebastian Vettel and the rest of the competitors here in Miami.”
Sebastian Vettel was forced to compete alone at the Race of Champions – but still came out on top
Wehrlein will now have to pass a medical examination ahead of next month’s F1 testing block, which starts on February 27 in Barcelona.
The 22-year-old had briefly been in line to replace Nico Rosberg at Mercedes after just one year at the top of motorsport with cash-strapped Manor Racing.
However, the team instead were able to secure the more experienced Valtteri Bottas from Williams and Wehrlein will instead race for Sauber in the 2017 season.
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He will line up for the team for the first time in competitive action when the season kicks off on March 26 with the Australian Grand Prix.