Abstract Objective Knee arthroplasty (KA) is an effective and cost-effective treatment for end-stage knee osteoarthritis. Despite high surgical success rates, as many as 25% of patients report compromised postoperative functioning, persistent pain, and reduced quality of life. The purpose of this study was to assess the predictive value of psychological factors in health functioning and quality of life, during a 6-month period after KA. Design A prospective observational study. Setting Surgery at two hospitals and follow-up was carried out through the domiciliary rehabilitation service. Subjects In total, 89 patients (age 70.27 ± 7.99 years) met the inclusion criteria. Method A test battery composed of Health functioning associated with osteoarthritis (WOMAC), Health-related quality of life (EQ-5D-5L), Anxiety and Depression (HADS), Pain attitudes (SOPA-B), Pain catastrophizing (PCS), and Fear of Movement (TSK-11) was assessed at 1 week, and 1, 3, and 6 months after surgery. A mixed effects linear model was used to estimate the effect of time and covariates. An exploratory factor analysis was used to identify the number of dimensions underlying the group of psychological measurements. Results In WOMAC model, anxiety level (F = 120.8), PCS (F = 103.9), depression level (F = 93.6) and pain score (F = 72.8) were the most influential variables. Regarding EQ-5D-5L model, anxiety level (F = 98.5), PCS (F = 79.8), depression level (F = 78.3) and pain score (F = 45) were the most influential variables. Pain score and the psychosocial variables of PCS, TSK, HADS-A, HADS-D, SOPA-B Emotion, SOPA-B Harm and SOPA-B Disability loaded in one single dimension. Conclusions Postoperative acute pain and psychosocial factors of pain catastrophizing, anxiety, depression, and pain attitudes might influence health functioning and quality of life during KA rehabilitation. Such factors could be gathered into one single dimension defined as pain-related psychologic distress.