The purpose of this study was to better understand the relationship between knee pain, locomotor functional status, and health-related quality of life (HRQoL) outcomes in osteoarthritic (OA) patients undergoing primary total knee arthroplasty (TKA). Nine OA patients were recruited. Pain, locomotor function, and HRQoL were evaluated one day before and 6 months after TKA by means of a visual analogue scale (VAS) for knee pain, the function score of the Knee Society (KS), the metabolic cost of gait (C), the total mechanical work during gait (Wtot), and the Medical Outcomes Study Short Form-36 Health Survey (MOS SF-36). Our results showed a decrease in knee pain and metabolic cost of gait and an improvement in quality of life. Moreover we showed a relationship between: (1) the VAS score for knee pain, the function score of the KS, and MOS SF-36 Physical Functioning, Role-Physical, and Bodily Pain subscales; and (2) the C, the Wtot, and the MOS SF-36 Vitality subscale.