The common cold is one of the major causes of work absenteeism. Former studies, based on artificial inoculation of rhinovirus, implicated psychological stress in the occurrence of this syndrome, either by increasing susceptibility to the virus or by causing the subject to overrate the perception of the symptoms. Nevertheless, few studies on the effect of stress on the naturally acquired common cold have been conducted. We carried out a 1-year prospective cohort study among the faculty and staff of a Spanish university (N = 1,149). By means of standardized questionnaires, validated in a random sample of the population, we assessed the relation between the occurrence of common cold episodes and exposure to four dimensions of stress: stressful life events, negative affect, positive affect, and perceived stress. All four aspects of stress were related to the occurrence of the common cold. Subjects with a high (fourth quartile) index of negative affect showed an incidence rate ratio of 3.7 (95% confidence interval = 2.2–6.2). The incidence rate ratios for the fourth quartile were 2.5 (95% confidence interval = 1.5–4.1) and 1.9 (95% confidence interval = 1.1–3.2) for perceived stress and stressful events, respectively. A high index of positive affect was associated with an incidence rate ratio of 0.6 (95% confidence interval = 0.3–1.0). These findings suggest that psychological stress is a risk factor for the common cold.