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Background Psychopathology and personality traits may influence the course of autoimmune disorders. With this prospective longitudinal cohort study, we aimed to assess personality, stress and depression in myasthenia patients who relapse and those who remain stable or improve (non-relapsers). Method We collected data from 155 consecutive adult patients with confirmed MG attending the Neuromuscular Clinic, Toronto General Hospital, between March 2017 and July 2018, for this study. Patients were assessed at baseline and 6 months, or at the time of MG relapse. At both visits, the patients were assessed clinically and were asked to complete self-administered questionnaires for disease severity, chronic stress and depression. Personality type was assessed at baseline only. Relapsing patients were defined as those patients with MGII score increasing by more than 5.5 points from visit 1 to visit 2. Results Relapsers had higher baseline scores for depression ( p  = 0.01) and the change in disease severity correlated with the change in depression score ( r  = 0.2534, p  = 0.0015, 95% CI: 0.098 0.3961). Higher levels of stress at baseline and neuroticism predicted higher relapse rates ( p  = 0.01 and p  < .0001, respectively). In the linear regression model, with change of the MGII score as the dependent variable, change in depression scores ( p  = 0.0004) and age ( p  = 0.03) predicted change in disease severity. Conclusions Since emotional factors and personality type may influence MG, attention to these factors might improve care in MG patients.