Purpose: People with osteoarthritis (OA) can also present with a number of comorbidities. Several studies have showed that individuals with knee OA are significantly more likely to have comorbidities than individuals without knee OA, both musculoskeletal as well as non-musculoskeletal conditions. Furthermore, studies have shown that the presence of co-existing medical conditions contributes to increased pain and poorer quality of life in people with knee OA. The purpose of this study was to assess the frequency of comorbidities in patients with knee OA entering the Good Life with osteoArthritis in Denmark (GLA:D®) Australia program and evaluate the impact of comorbidities on quality of life and pain. The association of other characteristics such as Body Mass Index (BMI), age and biological sex with pain and quality of life were also investigated. Methods: This was a cross-sectional nationwide registry-based study including patients with knee OA that entered the GLA:D®program in Australia from January 2018 until July 2019. The data in GLA:D®registry was collected through self-reported electronically answered questionnaires at time of entry. Baseline characteristics were extracted from the GLA:D®database regarding BMI, age, sex, affected joint and comorbidities. The examined patient-reported outcome measures (PROMs) consisted of the Knee injury and Osteoarthritis Outcome Score Quality of Life subscale (KOOS QoL), worst pain in the past month (worst pain) and average pain in the past month (average pain). To determine whether patient characteristics (comorbidity, BMI, age and sex) were correlated with the KOOS QoL-score and VAS-scores, Spearman’s rank correlation coefficients were calculated. Further, stepwise multiple linear regression analyses were applied on variables that were significantly associated (p<0.05) with any of the outcomes to conclude which characteristics were most linearly correlated with pain and joint-related quality of life. Adjusted R2 values less than 0.3 were considered very low, 0.3 to 0.5 low, >0.5 to 0.7 moderate and >0.7 strong. A P-value of <0.05 was considered statistically significant. Results: We included 1685 people, of which 1152 were women (68%), 528 were men (31%) and 5 did not specify gender (0.3%), with a median (inter-quartile range) age of 65 years (59-71). The majority of the participants had a BMI > 25; 38% were overweight (BMI 25-29,9) while 43% were obese (BMI ≥ 30). Fifty-nine percent had one or more comorbidities, the majority had 1-2 comorbidities (47% of the total population). Obesity was the most common comorbidity (43%) followed by high blood pressure (12.5%) and diabetes type 2 (5%). We found that BMI had a very low but statistically significant correlation with KOOS QoL (adjusted R2 0.044, p <0.001) and average pain (adjusted R20.028, p <0.001). None of the other included comorbidities in isolation had a statistically significant linear correlation with KOOS QoL, worst pain or average pain. However, cardiac disease, when combined with a higher BMI and lower age, showed a very low, but statistically significant correlation with lower KOOS QoL (adjusted R2 0.060, p <0.001) and a higher level of worst pain (adjusted R2 0.039, p <0.001). Conclusions: We found that BMI showed a small, but statistically significant correlation with KOOS QoL and average pain, indicating that a higher BMI is associated with higher levels of pain and poorer joint-related QoL. None of the other included comorbidities individually were associated with pain or KOOS QoL in people with knee OA. This suggests that the treatment of overweight and obesity in knee OA people could be essential in improving pain and quality of life.