Background:The high prevalence of pain and depression in persons with spinal cord injury (SCI) is well known. However the link between pain intensity, interference, and depression, particularly in the acute period of injury, has not received sufficient attention in the literature. Objective: To investigate the relationship of depression, pain intensity, and pain interference in individuals undergoing acute inpatient rehabilitation for traumatic SCI. Methods: Participants completed a survey that included measures of depression (PHQ-9), pain intensity ("right now"), and pain interference (Brief Pain Inventory: general activity, mood, mobility, relations with others, sleep, and enjoyment of life). Demographic and injury characteristics and information about current use of antidepressants and pre-injury binge drinking also were collected. Hierarchical multiple regression was used to test depression models in 3 steps: (1) age, gender, days since injury, injury level, antidepressant use, and pre-injury binge drinking (controlling variables); (2) pain intensity; and (3) pain interference (each tested separately). Results: With one exception, pain interference was the only statistically significant independent variable in each of the final models. Although pain intensity accounted for only 0.2% to 1.2% of the depression variance, pain interference accounted for 13% to 26% of the variance in depression. Conclusion: Our results suggest that pain intensity alone is insufficient for understanding the relationship of pain and depression in acute SCI. Instead, the ways in which pain interferes with daily life appear to have a much greater bearing on depression than pain intensity alone in the acute setting.