Background: Exergame-induced changes in the volume of brain gray matter have not been studied in fibromyalgia (FM). This study evaluates the effects of a 24-week exergame-based intervention on the gray matter volume of different brain structures in patients with FM through magnetic resonance imaging (MRI). Methods: A total of 25 FM patients completed 24 weeks of intervention program, and another 25 FM patients did not receive any intervention. T1-weighted MRI was used to assess brain volume, and FreeSurfer software was used to segment the brain regions. Results: No significant effects on gray matter volume of different structures and total gray matter were found. Conclusions: FM patients did not show significant changes in gray matter brain volume between the control and experimental groups after 24 weeks. FM patients showed significant relationships between peak oxygen consumption (pVO2) and the left and right regions of the hippocampus and the left and right regions of the amygdala.