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Norepinephrine (NE) neurons in the locus coeruleus (LC) make long-range projections throughout the central nervous system, playing critical roles in arousal and mood, as well as various components of cognition including attention, learning, and memory. The LC-NE system is also implicated in multiple neurological and neuropsychiatric disorders. Importantly, LC-NE neurons are highly sensitive to degeneration in both Alzheimer's and Parkinson's disease. Despite the clinical importance of the brain region and the prominent role of LC-NE neurons in a variety of brain and behavioral functions, a detailed molecular characterization of the LC is lacking. Here, we used a combination of spatially-resolved transcriptomics and single-nucleus RNA-sequencing to characterize the molecular landscape of the LC region and the transcriptomic profile of LC-NE neurons in the human brain. We provide a freely accessible resource of these data in web-accessible and downloadable formats., Competing Interests: LW, HD, SK, AS, KM, MT, RB, JK, SP, TH, LC, KM, KM, SH No competing interests declared, MT The authors declare that they have no competing interests. Matthew N. Tran (MNT) is now a full-time employee at 23andMe and whose current work is unrelated to the contents of this manuscript. His contributions to this manuscript were made while previously employed at the Lieber Institute for Brain Development (LIBD), (© 2023, Weber, Divecha et al.)