We examined whether interpersonal rejection sensitivity (IRS)—the hallmark of atypical depression – prospectively predicted burnout, controlling for baseline symptoms, history of depressive disorders, antidepressant intake, gender, age, and length of employment (mean between-assessment duration: 21 months; n = 578; 74% female). IRS was related to a 119% increased risk of burnout at follow-up. Three of four burned out participants reported to be affected by IRS, or 2.5 times the rate observed in participants with no (or subthreshold) burnout symptoms. Our study highlights a dispositional factor in burnout’s etiology also known to be a key component of atypical depression’s etiology. The ontogenesis of individual vulnerabilities to burnout should be further examined in future research.