Substance use (SU) has been linked to alterations in reward processing in the ventral striatum (VS). However, less is known about how SU relates to striatal activation and connectivity during social rewards (e.g., positive peer feedback). In this pre-registered study, we hypothesized that SU would be associated with activation and functional connectivity of the VS during receipt of social rewards. Participants (N=44) underwent two fMRI tasks to isolate neural response to social and monetary rewards. The tasks involved choosing between two stimuli: either two purported peers, with the goal of identifying the peer who liked the participant (social); or two doors, with the goal of identifying the door containing a $0.50 prize (monetary). We predicted that VS activation in response to social rewards would be correlated with SU, independent of reward sensitivity (RS); however, an exploratory whole-brain analysis revealed SU was related to activation in the temporoparietal junction instead. Moreover, results showed that aberrant RS blunts the relationship between SU and striatal activation during receipt of rewards, regardless of their domain. Psychophysiological interaction (PPI) analysis demonstrated that SU was associated with decreased connectivity between the VS and dorsomedial prefrontal cortex for social rewards, independent of RS. Exploratory analyses further revealed that RS is associated with increased connectivity between the VS and ventromedial prefrontal cortex during social rewards. Taken together, these findings shed light on the relationships between potential risk factors for developing substance use disorder.