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Background: Mixed martial arts (MMA) fighters, due to exposure to repetitive head impacts, are at risk for brain atrophy and neurodegenerative sequelae. Simultaneously, motor skills training and cognition-rich activities have been linked with larger regional brain volumes. The majority of an MMA fighter's sporting activity occurs during practice (e.g., sparring) rather than formal competition. This study, therefore, aims to be the first to explore regional brain volumes associated with sparring in MMA fighters. Methods: Ninety-four active, professional MMA fighters from the Professional Fighters Brain Health Study met inclusion criteria for this cross-sectional analysis. Adjusted multivariable regression analyses were utilized to examine the relationship between the number of sparring practice rounds per week during typical training and a select number of regional brain volumes (i.e., caudate, thalamus, putamen, hippocampus, amygdala). Results: A higher number of weekly sparring rounds during training was significantly associated with larger left (beta = 13.5 µL/round, 95% CI 2.26–24.8) and right (beta = 14.9 µL/round, 95% CI 3.64–26.2) caudate volumes. Sparring was not significantly associated with left or right thalamus, putamen, hippocampus, or amygdala volumes. Conclusions: More weekly rounds of sparring was not significantly associated with smaller volumes in any of the brain regions studied in active, professional MMA fighters. Sparring's significant association with larger caudate volume raises questions about whether fighters who spar more experience attenuated trauma-related decreases in caudate volume relative to fighters who spar less, whether fighters who spar more experience minimal or even positive changes to caudate volume, whether baseline differences in caudate size may have mediated results, or whether some other mechanism may be at play. Given limitations inherent to the cross-sectional study design, more research is needed to further explore the brain effects of sparring in MMA. [ABSTRACT FROM AUTHOR]