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Objective: Obesity and depression are major, inter-related health concerns for men, yet many do not receive support to manage these conditions. This study investigated whether a self-guided, eHealth program (SHED-IT: Recharge) could reduce weight and depressive symptoms in men with overweight or obesity and low mood. Method: Overall, 125 men [Body Mass Index (BMI) 25–42 kg/m2] with depressive symptoms [Patient Health Questionnaire-9 (PHQ-9) score ≥5] were recruited for a 6-month RCT. Men were randomized to (a) the SHED-IT: Recharge group (n = 62) or (b) a wait-list control group (n = 63). The 3-month program included printed and online resources (e.g., website, interactive modules). It was adapted from an evidence-based weight loss program for men to include an additional focus on "mental fitness". The primary outcomes were weight (kg) and depressive symptoms (PHQ-9) at 3 months. Men were assessed at baseline, 3 months (post-intervention), and 6 months. Intention-to-treat linear mixed models examined program outcomes. Results: At 3 months, medium-sized treatment effects were detected for both weight, adjusted mean difference −3.1 kg, 95% CI [−4.3, −1.9], d = 0.9, and depressive symptoms, adjusted mean difference −2.4 units, 95% CI [−4.0, −0.9], d = 0.6. These effects were maintained at 6 months and supported by sustained improvements in other health outcomes. Conclusions: A self-guided, eHealth program that combined behavioral weight loss advice with mental health support decreased weight and depressive symptoms in men. Integrated interventions targeting physical and mental health may be an effective strategy to engage and support men with overweight or obesity and low mood. What is the public health significance of this article?: In this randomized trial, an unguided, eHealth intervention improved the physical and mental health of men with overweight or obesity, and mild-to-severe depressive symptoms. Although the 3-month program was completely self-directed, men in the intervention group reduced their mean weight and depressive symptoms by 3.3 kg and 46% at post-intervention, respectively. These changes were significantly greater than those observed in a wait-list control group (−0.2 kg, 19% reduction in symptoms) and were maintained at 6-month follow-up. Integrated online interventions targeting men's physical and mental health could play a key role in preventing and treating depression in men. [ABSTRACT FROM AUTHOR]