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. (PsycInfo Database Record (c) 2021 APA, all rights reserved).