Milk and dairy products are known to contain various bioactives with potential anti-inflammatory and immune modulating effects. Previous research has indicated that milk produced from hyperimmunized cows provided meaningful health benefits to individuals suffering from varying degrees of osteoarthritis and rheumatoid arthritis. PURPOSE: To examine the impact of a proprietary milk protein concentrate on joint discomfort and physical function, exercise performance, quality of life and various measures of affect. METHODS: Non-osteoarthritic men (42.5 ± 8.9 years, 176.7 ± 6.7 cm, 89.9 ± 11.5 kg, 28.8 ± 3.5 kg/m 2, n = 30) and women (46.4 ± 9.6 years, 163.1 ± 8.2 cm, 72.2 ± 13.1 kg, 27.2 ± 5.3 kg/m 2, n = 28) with mild to moderate knee pain during physical activity were randomized in a double-blind, placebo-controlled fashion to consume daily either a placebo (PLA) or proprietary milk protein concentrate (MP) for a period of 8 weeks. Participants completed a functional capacity test pre and post-supplementation and completed visual analog scales (VAS), a 6-min walking test, WOMAC and profile of mood states (POMS) to assess changes in joint health, discomfort, physical function, exercise performance and affect. Mixed factorial ANOVA was used for all statistical analysis and significance was set a priori at p ≤ 0.05. RESULTS: Distance covered in the 6-min walking significantly improved 9% in MP versus 2% in PLA (mean difference: 110 ± 43 m, p = 0.012) in addition to 11 WOMAC components and 5 VAS reflective of MP improving joint health, discomfort and joint stability (all p < 0.05 vs. PLA). Additionally, MP also improved overall perceptions of neck and back health compared to PLA. Serum and whole blood indicators of clinical safety remained within normal ranges throughout the study. CONCLUSIONS: In comparison to placebo, daily doses of proprietary milk protein concentrate yielded improvements in several components of the WOMAC, multiple visual analog scales indicative of joint health and stability, discomfort and pain, as well as significant improvements in distance covered during a 6-min walking test. Supplementation was well tolerated with no significant changes in whole-blood or serum markers of clinical safety.