The major famous degenerative joint disease is osteoarthritis (OA), which leads to disability, reduced motion, pain, swelling, and crepitus. Thus, this research aimed to determine the statuses of oxidative stress (OS) and antioxidants in blood patients with primary OA and to compare serum levels of some inflammatory markers between control and knee OA patients groups. In this case-control study, 126 knee OA patients and 49 control individuals were taken, who visited the Center of Rheumatoid in Duhok city, Kurdistan region of Iraq. For the participant’s information, a study questionnaire was employed. Serum total bilirubin (TBIL), uric acid (UA), catalase, peroxynitrite (PN), malondialdehyde (MDA), and ceruloplasmin (CP) were evaluated. Some inflammatory markers were measured, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Also, body mass index (BMI) was measured. In the present study, the % of the control group was 28% and patients groups were 29.71, 28, and 14.29% for mild, moderate, and severe cases, respectively. The mean values of MDA and CP showed significant differences between knee OA and control groups. On the other hand, the mean values of catalase, PN, UA, and TBIL showed no significant differences among control and knee OA groups. A significant difference was found among control and knee OA groups for ESR, but CRP was non-significant. In the current study, elevated levels of lipid-peroxidation and CP in patients with knee OA were observed. OS may be involved in OA.