The roles of NK cells in human melanoma remain only partially understood. We characterized NK cells from peripheral blood ex vivo by flow cytometry obtained from late stage (III/IV) melanoma patients. Interestingly, we found that the abundance of CD56bright NK cells negatively correlate with overall patient survival, together with distant metastases, in a multivariate cox regression analysis. The patients' CD56bright NK cells showed upregulation of CD11a, CD38 and CD95 as compared to healthy controls, pointing to an activated phenotype as well as a possible immune regulatory role in melanoma patients. After stimulation in vitro, CD56bright NK cells produced less TNFα and GMCSF in patients than controls. Furthermore, IFNγ production by the CD56bright NK cells correlated inversely with overall survival. Our results highlight that abundance and function of CD56bright NK cells are associated with melanoma patient survival, emphasizing the potential of NK cell subsets for biomarker discovery and future therapeutic targeting.