Cocaine use disorder (CUD) is becoming more prevalent in females, but research into sex-dependent neural mechanisms underlying cocaine use is lacking. Accordingly, the main objective of the current study was to investigate sex-dependent differences in the neural correlates of cocaine and emotional cue reactivity within regular cocaine users (CUs) and non-cocaine-using controls (non-CUs). A cocaine and emotional cue-reactivity fMRI paradigm was completed by 31 male and 26 female CUs and 28 male and 26 female non-CUs. A region of interest analysis was performed to test for sex-specific differences in cocaine and emotional cue-induce activation of the dorsal striatum (DS), ventral striatum (VS), amygdala, and dorsal anterior cingulate cortex (dACC). Although there were no significant sex-dependent differences between CUs and non-CUs in neural cocaine and emotional cue reactivity, exploratory analyses demonstrated that the association between cocaine cue-induced activation of the DS and amygdala and cocaine use severity was significantly moderated by sex: while this association was positive female CUs, it was negative in male CUs. Similarly, the relationship between emotional cue-induced activation of the dACC and VS and years of regular cocaine use was also moderated by sex: while this association was negative in female CUs, it was positive in male CUs. While exploratory, the current findings highlight the importance of taking into account sex differences when studying the underlying mechanism of CUD, as this may pave the way for the identification of sex-specific treatment targets.