The aversive properties associated with drugs of abuse influence both the development of addiction and relapse. Cocaine produces strong aversive effects after rewarding effects wear off, accompanied by increased firing in the lateral habenula (LHb) that contributes to downstream activation of the rostromedial tegmental nucleus (RMTg). However, the sources of this LHb activation are unknown, as the LHb receives many excitatory inputs whose contributions to cocaine aversion remain uncharacterized. Using cFos activation and in vivo electrophysiology in male rats, we demonstrated that the rostral entopeduncular nucleus (rEPN) was the most responsive region to cocaine among LHb afferents examined, and that single cocaine infusions induced bi-phasic responses in rEPN neurons, with inhibition during cocaine’s initial rewarding phase transitioning to excitation during cocaine’s delayed aversive phase. Furthermore, rEPN lesions reduced cocaine-induced cFos activation by two-fold in the LHb and by a smaller proporti...