The Dockers confirmed on Monday scans revealed Pearce suffered a new fracture in his left forearm, while Papley will be sidelined for four to six weeks with a medial ankle ligament injury.
Pearce was subbed out in their Melbourne clash after a knock to his surgically repaired arm resulted in a new fracture to his radius bone.
The 29-year-old defender had already spent four weeks on the sidelines recovering from a fracture in the same bone suffered against Gold Coast in round 15.
His absence is a hefty blow to Fremantle's top-four aspirations with just five rounds left of the home-and-away season.
"Unfortunately, Alex has suffered another fracture of his left radius after an incident in the third quarter against Melbourne," Fremantle football boss Joe Brierty said.
"It's really disappointing for Alex who made such a strong return in the opening three quarters of the game.
"Our medical team will now consult specialists to consider the best intervention in collaboration with Alex and we will then have a better understanding of Alex's return to play timeline."
Tom Papley leaves the Gabba, followed by Swans teammates, in discomfort after his injury. (Darren England/AAP PHOTOS)
Papley's injury comes as the ladder-leading Swans battle to find their form, having lost three of their past four games.
The 28-year-old was seen in a moonboot during Sydney's two-point loss to the Brisbane Lions after twisting his right ankle when he fell in a second-quarter marking contest.
Further assessment confirmed the extent of his injury.
Papley has kicked 30 goals across 18 games this season, sitting equal-second with Will Hayward for the Swans behind Joel Amartey's 35.
Hayward will be a test to play against the Western Bulldogs on Sunday after also suffering an ankle injury.
The forward was able to finish the match at the Gabba despite sustaining a lateral ankle sprain in the second term.
Will Hayward reaches for his left ankle during the Swans' tight loss to the Lions. (Darren England/AAP PHOTOS)
Veteran defender Dane Rampe will also be assessed ahead of their Bulldogs match.
Rampe was substituted out with calf tightness minutes before Papley injured his ankle.
Brisbane's Harris Andrews will miss their derby with rivals Gold Coast after entering concussion protocols.
Andrews suffered a head knock during the final seconds of their Sydney match, having just minutes earlier returned to the field after successfully passing a concussion evaluation for a separate incident.
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