Although it is widely recognized that stress plays a key role in the pathophysiology of schizophrenia, little is known regarding the particular types of stress patients experience. Less is known about the interplay among stressful events, personality mediators, and emotional responses. In this study, we investigated 10 stress dimensions in 29 patients with schizophrenia and 36 healthy volunteers using the Derogatis Stress Profile (DSP), and the relationship between these dimensions and symptoms in patients. Overall, patients had an approximate 0.75 standard deviation increase in stress compared with healthy volunteers. Significant increases in stress among patients compared with healthy volunteers were observed specifically in areas related to domestic environment, driven behavior, and depression, but not in health, attitude posture, time pressure, relaxation potential, role definition, hostility, or anxiety. More DSP-rated depression among patients correlated significantly with greater negative symptom severity. Patients with a shorter duration of antipsychotic drug exposure had significantly greater hostility than did patients with a longer duration of exposure, but did not differ in any other dimension. Continued investigation of domestic environmental stressors, driven behavior, and depression may be useful in identifying high-risk groups, and understanding symptom exacerbation and precipitants of relapse in patients already diagnosed with schizophrenia.