Major depressive episodes once were thought to be a natural part of the recovery and adaptation from acute spinal cord injury (SCI). Others disagree and note that a variety of affective and cognitive reactions, which may or may not include dysphoria, occur after SCI. Studies which have sought to determine the actual prevalence of major depression among SCI patients have varied in their definition of depression, severity of episode, and use of instruments to diagnose depression. In an attempt to identify the prevalence and potential factors associated with abnormal depression ratings in SCI patients, the Zung Self-Rating Depression Scale (ZUNG), a 20-item inventory of somatic and affective qualities of depression, was administered an average of 63 days post-injury to 58 acute SCI patients at two regional SCI care centers. A group of 51 volunteer healthy subjects, comparable for age and geographic location, served as a control group. The mean ZUNG scores were 37.1 ± 1.1 (± 1 s.e.) for the control group and 49.0 ± 1.3 for the SCI patients (t (107), p < 0.0001). Several factors, including age, years of education, level of injury (paraplegic versus quadriplegic), etiology of injury (violent versus non-violent), presence of acute closed head injury, or recent history of alcohol or substance abuse, had no association with ZUNG scores. Since undiagnosed and untreated depression may compromise a SCI patient's adaptation to injury and motivation during rehabilitation, abnormally elevated ZUNG scores may help to determine which patients might require more focused psychological assessment and treatment.