Approximately 17,000 new cases of spinal cord injury (SCI) are reported annually in the United States. Rehabilitation from SCI involves substantial mental, emotional, and physical challenges. Using a randomized controlled trial design, we assessed the efficacy of animal-assisted therapy (AAT) as an aid in rehabilitation following a SCI. We hypothesized that patients with SCI undergoing rehabilitation occupational therapy with AAT would demonstrate greater positive shifts in mood and outlook, reduced pain, and reduced stress compared with patients exposed to the same rehabilitation therapy but without AAT. Over four sessions of occupational therapy, 31 patients completed standard rehabilitation activities (control group) or rehabilitation activities integrating an animal therapy team (treatment group). Patients completed the Positive and Negative Affect Schedule (PANAS) and Numerical Rating Scale (NRS) at each session, had salivary cortisol sampled at the second session, and completed the Brief Pain Inventory at study baseline and exit. Data were analyzed using repeated measures ANOVAs and t-tests. The results revealed a small but significant effect of animal-assisted therapy on self-reported negative affect. Findings for group differences on positive affect, stress, and pain unpleasantness were null, although non-significant findings were in the hypothesized direction for several variables and yielded small effect sizes. Continued research is needed on the influence of AAT on mood improvement, stress reduction, and ultimately improved physical health outcomes during rehabilitation after SCI.