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Objective Exercise is recommended as a main treatment in fibromyalgia. However, many people have limited exercise tolerance and report exacerbated pain and fatigue during and following a bout of exercise. This study examined the local and systemic changes in perceived pain and fatigue during exercise and through the 3-day recovery following isometric and concentric exercises in people with and without fibromyalgia. Methods Forty-seven participants with a physician diagnosis of fibromyalgia (44 women; mean age [SD] = 51.3 [12.3] years; mean body mass index [SD] = 30.2 [6.9]) and 47 controls (44 women; mean age [SD] = 52.5 [14.7] years; mean body mass index [SD] = 27.7 [5.6]) completed this prospective, observational cohort study. A bout of submaximal resistance exercise (isometric and concentric) was performed localized to the right elbow flexors on 2 separate days. Baseline attributes (pain, fatigue, physical function, physical activity, and body composition) were assessed prior to exercise. Primary outcomes were: change in perceived pain and fatigue (0 to 10 on the visual analog scale) in the exercising limb and whole body during recovery with movement (immediately, 1 day following exercise, and 3 days following exercise). Secondary outcomes were perceived pain and exertion during exercise performance and pain and fatigue at rest during recovery. Results Following a single bout of isometric or concentric exercise, there was increased perceived pain (η p 2 = 0.315) and fatigue (η p 2 = 0.426) in the exercising limb, which was greater in people with fibromyalgia (pain: η p 2 = 0.198; fatigue: η p 2 = 0.211). Clinically, relevant increases in pain and fatigue during exercise and through the 3-day recovery occurred in individuals with fibromyalgia only. Concentric contractions led to greater perceived pain, exertion, and fatigue during exercise compared with isometric exercise for both groups. Conclusions People with fibromyalgia experienced significant pain and fatigue in the exercising muscle during recovery from low-intensity and short-duration resistance exercise, with greater pain during concentric contractions. Impact These findings highlight a critical need to assess and manage pain and fatigue in the exercising muscles of people with fibromyalgia up to 3 days following a single bout of submaximal resistance exercise. Lay Summary If you have fibromyalgia, you might have significant pain and fatigue up to 3 days following an exercise bout, with the pain and fatigue localized to the exercising muscles and no changes in whole-body pain. [ABSTRACT FROM AUTHOR]