Opioids are indispensable analgesics. However, they produce harmful side effects, including addiction and respiratory depression, that drive the ongoing opioid epidemic. Distinguishing the neural circuits driving opioid analgesia from circuits that produce undesirable side effects may lead to safer and more effective pain treatments. Opioids target the mu opioid receptor (MOR), an inhibitory G protein-coupled receptor expressed by a variety of neurons throughout the nervous system. The different behavioral effects of opioids result from MOR signaling in distinct brain regions, however, the precise cell-types that drive these effects are unknown. Furthermore, although women experience diminished pain relief from opioids compared to men, whether MOR-expressing neurons differ between sexes is unknown. Generating a molecular catalog of MOR-expressing neurons throughout the brain would provide a means to distinguish and modulate specific opioid-sensitive circuits that drive disparate opioid effects. Here, we used deep single-cell RNA-sequencing (scRNA-seq) from neurons across over 100 carefully dissected brain regions in both male and female mice to characterize cells expressing Oprm1, the gene that encodes MOR. Although we detected Oprm1+ neurons in virtually all regions, the proportion of Oprm1+ cells and RNA abundance varied greatly throughout brain regions and between sexes. We used unsupervised clustering and differential gene expression to characterize Oprm1-enriched neurons. From these analyses we identified marker genes and genes encoding neuromodulatory proteins that are coexpressed by Oprm1+ neurons at brain-wide, regional, and cell-type-specific scales. Together, these data elucidate the organization of opioid-sensitive neurons throughout the brain to induce analgesia without eliciting unwanted side effects. 5R01DA054583-02.