The unprecedented development and ubiquity of sports betting constitute an emerging public health concern. It is crucial to provide markers that could help to better identify people experiencing sports betting-related harms. The current study investigated whether problem gambling status, sports betting passion, and trait-self-control modulate brain reactivity to sports betting cues. Sixty-five frequent sports bettors (35 "nonproblem bettors" and 30 "problem bettors") were exposed to cues representing real upcoming sport events (with varying levels of winning confidence) that were made available or blocked for betting, during functional magnetic resonance imaging (fMRI) recording. Sports betting passion and trait-self-control were assessed using self-report scales. Sport events nonavailable for betting elicited higher insular and striatal activation in problem bettors, as compared with nonproblem bettors. Within a large cluster encompassing the ventral striatum, hippocampus, and amygdala, lower trait-self-control was associated with increased brain reactivity to sport events with high levels of winning confidence that were nonavailable for betting. No significant effect of sports betting passion was observed. These findings suggest that sports bettors' brain reactivity to gambling unavailability might be a relevant marker of sports betting-related harms, as well as of blunted trait-self-control.