Background/Objectives - Frailty is highly prevalent with increasing age. Based on the concept of depression as a disorder of accelerated aging and its association with inflammation and metabolic dysregulation, we examined whether frailty measures at baseline and over time differed between immuno-metabolic subtypes of late-life depression. Methods - Clinical cohort study in primary and secondary mental health care with two-year follow-up. In total 359 depressed older patients (≥ 60 years) classified in four immuno-metabolic subgroups by latent profile analysis. We compared frailty measures at baseline and two-year follow-up adjusted for confounders between immuno-metabolic based depressed subgroups. Frailty measures included the frailty index, physical frailty phenotype, and two proxies (handgrip strength, gait speed). Results - At baseline, the relatively healthy depressed subgroup (n = 181) performed best on all frailty markers. While frailty markers worsened over time, the two-year course did not differ between the subgroups for any of these markers. Conclusion - The more severe immuno-metabolic dysregulation present in late-life depression, the more frail. Nonetheless, as trajectories over time did not differ between subgroups, the difference probably emerged at midlife. Future studies should examine whether geriatric assessment might become relevant at earlier ages in specialized mental health care.