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Neuroendocrine biomarkers have long been studied in the context of electroconvulsive therapy (ECT). We prospectively assessed serum oxytocin change and moderators thereof in an exploratory study of patients receiving ECT.Serum oxytocin concentrations were assessed immediately before and 1 to 3 minutes after the first ECT in 33 patients with schizophrenia (n = 14), other nonaffective psychosis (n = 6), mania (n = 10), and depression (n = 3) who received 6 to 7 bitemporal, brief-pulse ECTs. Change in serum oxytocin was assessed in the sample as a whole, and as a function of age, sex, diagnosis, and treatment response. The primary outcome was change in serum oxytocin in the overall sample.There was much variation across patients; oxytocin concentrations increased marginally by a mean (standard deviation) (M [SD]) of 6.4 (82.7) pg/mL (P = 0.43). The M (SD) change was −8.2 (85.0) pg/mL in patients with schizophrenia and other nonaffective psychoses (P = 0.84). There was no significant correlation between change in Brief Psychiatric Rating Scale scores and change in oxytocin concentrations in patients with schizophrenia, other nonaffective psychoses, and mania (ρ = 0.10, P = 0.61). Serum oxytocin rose in men, after ECT, and fell in women (P = 0.01).Change in serum oxytocin immediately after the first ECT in a course may not be a useful biomarker of ECT action. This is the first report on the subject in a sample comprising mostly patients with nonaffective psychosis and mania rather than depression. We discuss our findings in the light of previous research and offer general conclusions about the field.