MMAFighting.com first reported that Overeem had withdrawn. The UFC has not announced if dos Santos will remain on the card, now without its co-main event.
This is the second time the UFC has booked the matchup, only to see it fall through. The two were originally paired in a heavyweight title fight at UFC 146 last May, but Overeem was denied a license to fight in Nevada after he failed a random drug test in Las Vegas.
Overeem (36-12) was last seen in the Octagon at UFC 156, where he suffered a surprising third-round knockout loss to Antonio Silva. It was the former Strikeforce champion's first loss since 2007.
Dos Santos (15-2) also is looking to rebound from a recent loss. He relinquished the UFC belt in December after a unanimous decision loss to Cain Velasquez. The Brazilian successfully defended the belt once, defeating Frank Mir at UFC 146.