Background and Objectives: Osteoarthritis is an inflammatory and degenerative joint disease, causing pain, musculoskeletal disorders and would affect functionality, daily life activities and quality of life. Comparing the effects of ultrasound and microwave physiotherapy treatments on knee osteoarthritis by measuring osteocalcin level and erythrocyte sedimentation rate in blood. Methods: In a cross-sectional study conducted in in Hawler teaching hospital and Rzgari teaching hospital over the period December 2018 to May 2019, 30 patients with knee joint osteoarthritis were recruited. Half of them were provided with ultrasound physiotherapy treatment, and half with microwave physiotherapy treatment. The level of serum osteocalcin and erythrocyte sedimentation rate in blood were measured in both groups before and after the treatment with lasted for one month. The collected data were analyzed through paired and independent samples t-test using Statistical Package for the Social Sciences (version 18). Results: Most of the patients (73.3%) were females. Right knee osteoarthritis was the most prevalent with 13 patients, followed by bilateral knee osteoarthritis with 10 cases, and left knee osteoarthritis with 7 patients. The results indicated that ultrasound physiotherapy treatment had a significant effect on the level of serum osteocalcin (p=0.01) and erythrocyte sedimentation rate in blood (p=0.000). It was also seen that microwave physiotherapy treatment had a significant effect on erythrocyte sedimentation rate in blood (p=0.000), while its effect on the level of serum osteocalcin was not significant (p=0.53). Conclusion: Based on the data collected from the present study, there is sufficient evidence to indicate that ultrasound and microwave physiotherapy interventions can reduce pain and improve function in those with knee OA.