Background: Students often simultaneously deal with shifting support networks, stressful life changes and psychological distress which may affect academic achievement. Methods: 285 students completed the General Health Questionnaire (GHQ-12) to assess depression and the Computerized Life Events Assessment Record (CLEAR), to establish life events and supportive relationships. Module grades were used to measure academic achievement. A general linear model was used with student grade as the dependent variable and life events, depression and supportive relationships as independent variables. Confounding variables included age and sex. Results: A three-way interaction between life events, depression and lack of supportive relationships was found. It indicated the performance of depressed students depended on whether they had supportive relationships and that this interaction also depended on whether they had experienced a life event in the past year. Conclusions: Universities need to provide more support to students with life stress as they transition into university life.