Blending polyunsaturated oils with highly saturated or monounsaturated oils has been studied extensively; however, in literature there is negligible information available on the blending of refined cottonseed oil with palm olein oil. Blending could enhance the stability and quality of cottonseed oil during the frying process. In the present study, the effects of frying conditions on physicochemical properties of the palm olein-cottonseed oil blends (1:0, 3:2, 1:1, 2:3, and 0:1, w/w) were determined and compared to the pure oils. The frying process of frozen French fries was performed in duplicate at 170 ± 5°C for 10 h without interruption. The oil degradations were characterized during deep-frying applications; peroxide, free fatty acid, and iodine value by standardized methods, fatty acid profile by using a gas chromatography-flame ionization detector, polar and polymeric compounds by using the high-performance size exclusion chromatography/evaporative light scattering detector technique. The present study clearly indicated that the oxidative and frying performances of pure palm olein oil and cottonseed oil significantly improved by blending application. Results clearly indicated that the frying performance of cottonseed oil significantly improved by the blending with palm olein oil. Except that free fatty acid content, all the physicochemical variables were significantly influenced by type of pure and blend oils. By increasing the proportion of palm olein oil in cottonseed oil, the levels of polyunsaturated fatty acids decreased, while saturated fatty acid content increased. The progression of oxidation was basically followed by detecting polar and polymeric compounds. The fastest increments for polar and polymeric compounds were found as 6.30% level in pure cottonseed oil and as 7.07% level in 40% cottonseed oil:60% palm olein oil blend. The least increments were detected as 5.40% level in 40% cottonseed oil:60% palm olein oil blend and 2.27% level in 50% cottonseed oil:50% palm olein oil blend. These levels were considerably below the acceptable levels recommended by the official codex. Therefore, the present study suggested that blending of cottonseed oil with palm olein oil provided the oil blends (50% cottonseed oil:50% palm olein oil and 40% cottonseed oil:60% palm olein oil, w/w) with more desirable properties for human nutrition.