OBJECTIVE To assess clinical effects of an omega-3 fatty acid and protein-enriched diet, physical rehabilitation, or both in dogs following tibial plateau leveling osteotomy (TPLO) and arthroscopic surgery for cranial cruciate ligament (CCL) disease. DESIGN Randomized, prospective clinical trial. ANIMALS 48 dogs with unilateral CCL disease. PROCEDURES Dogs were randomly assigned to receive a dry omega-3 fatty acid and protein-enriched dog food formulated to support joint health (test food [TF]), a dry food formulated for maintenance of adult dogs (control food [CF]), TF plus rehabilitation (TF-R), or CF plus rehabilitation (CF-R). Data collected over 6 months included body weight, body condition score, ground reaction force data, tibial plateau angle, limb circumference measurements, subjective pain and lameness scores assigned by surgeons and dog owners, and daily activity measured by accelerometry. RESULTS Peak vertical force and vertical impulse were greater after surgery for dogs in the TF groups than in the CF groups; peak vertical force was greater after surgery in dogs that underwent rehabilitation than in those that did not. Owner scores indicated lower frequencies of lameness and signs of pain during some activities for the TF group, compared with other groups, and for the TF-R and CF-R groups, compared with the CF group. Sedentary time decreased and time spent in light-to-moderate or vigorous activity increased in all groups over time. Rehabilitation was significantly associated with greater time spent in light-to-moderate activity, regardless of diet. CONCLUSIONS AND CLINICAL RELEVANCE Feeding the TF and providing physical rehabilitation during the first 6 months after TPLO were associated with improvements in some indices of clinical outcome and function in dogs. Significant interactions between time and some outcome variables were observed, indicating further research is warranted.