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Introduction Osteoarthritis (OA) is a worldwide, disabling condition, more prevalent in older people. Although anxiety and depression disorders are common in OA and may affect compliance with treatment, both disorders are still underrecognized and undertreated. The present study aimed to screen for anxiety and depression among patients with primary knee OA, and to study the relationship between Hospital Anxiety and Depression Scale (HADS) score and different disease parameters. Material and methods Fifty patients fulfilling primary knee OA classification criteria were recruited for the study, and 50 age- and sex-matched healthy individuals served as a control group. Medical history was taken, clinical examination was done, and pain intensity was assessed using the Visual Analogue Scale. The 6-minute walk test was used for functional status assessment, and plain X-ray knees were scored according to the Kellgren and Lawrence classification system. Participants completed the HADS questionnaire. Results Twenty-nine patients were female (58%) and 21 were male (42%). The mean HADS score was significantly higher in OA patients than controls ( p = 0.001). The mean HADS-A (Anxiety) score was statistically significantly higher in OA patients than controls ( p < 0.001). Anxiety was more frequent in patients (44%) than in controls (10%) ( p < 0.001). In regression analysis, female sex could be considered as a predictor for each of HADS-A and HADS-D (Depression) (b: 0.4, 0.3; t : 3.28, 2.2; p = 0.002, 0.03; CI: 1.3–5.6, 0.2–4.4), respectively, while knee giving way was considered as a predictor for HADS-A (b: 0.34, t : 2.8, p = 0.007, CI: 0.96–5.87). Conclusions The results of the present study showed that anxiety level rather than depression was significantly higher in patients with primary knee OA than in controls. Female sex could be considered as a predictor for each of HADS-A and HADS-D, while knee giving way was considered as a predictor for HADS-A.