Improving our ability to accurately predict individual risk for depression would have profound public health benefits. While there has been growing interest in understanding the relation between measures of positive emotion, such as well-being, and depression, it is not clear whether low well-being is an independent predictor of short term depression risk. We assessed whether low well-being is a risk factor for depressive symptoms. Medical internship is a well-established period of stress when levels of depressive symptoms increase dramatically. 1621 individuals beginning medical internship were assessed for well-being, depressive symptoms, and a set of psychological and demographic traits prior to starting internship year and again for depressive symptoms at 3 month intervals during the year. Low subjective well-being significantly predicted increased depression symptom scores during the stress of medical internship and accounted for individual level inter-variability in depression symptom trends across time. Assessing well-being may have utility in predicting future depression risk.