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Objective To determine whether a single low dose of esketamine administered after childbirth reduces postpartum depression in mothers with prenatal depression. Design Randomised, double blind, placebo controlled trial with two parallel arms. Setting Five tertiary care hospitals in China, 19 June 2020 to 3 August 2022. Participants 364 mothers aged ≥18 years who had at least mild prenatal depression as indicated by Edinburgh postnatal depression scale scores of ≥10 (range 0-30, with higher scores indicating worse depression) and who were admitted to hospital for delivery. Interventions Participants were randomly assigned 1:1 to receive either 0.2 mg/kg esketamine or placebo infused intravenously over 40 minutes after childbirth once the umbilical cord had been clamped. Main outcome measures The primary outcome was prevalence of a major depressive episode at 42 days post partum, diagnosed using the mini-international neuropsychiatric interview. Secondary outcomes included the Ed

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