Hayden, who had surgery on his fractured left foot last November, has been ruled out for at least the first eight weeks of the season, with that possibly extending out to as much as 12 weeks.
The 30-year-old played all but one game in 2010, including Fremantle's two finals, earning a one-year contract extension for the 2011 season.
However, the classy defender has a long injury history, with a string of hamstring injuries, a broken leg and a punctured lung restricting him in 2008 and 2009.
Hayden is one of 11 Fremantle players ruled out for the side's round one clash against the Brisbane Lions at the Gabba, including five of the side's nominal best line-up.
Promising mature-age recruit Tendai Mzungu, who had been earmarked to fill the half-back role vacated by Hayden, has been ruled out for eight to 10 weeks with a knee injury.
The WAFL recruit suffered medial ligament damage and bone bruising to his left knee in Fremantle's NAB Challenge win against West Coast at the weekend.
Michael Barlow (leg), Matt de Boer (hamstring), Garrick Ibbotson (ankle) and Anthony Morabito (knee) are also missing from Fremantle's best side.
The long injury list will present opportunities for young players, with draftee Viv Michie impressing throughout his first pre-season.
Young players Dylan Roberton and Jay van Berlo will also have opportunities to cement spots in the team.
Midfield recruit Nick Lower is set to be the club's nominated rookie for the 2011 season with the former Port Adelaide half-back staking a strong claim for round one selection.