The main goal of the present study was (i) to determine the formation of degradation products in cottonseed oil (CSO) blends during deep frying process by adsorption and high performance size exclusion chromatography techniques and (ii) to evaluate the impacts of food additives on total polar (TPC) and polymeric compound (PTAG) formation using a chemometric approach. In order to prepare the frying CSO blends; ascorbic palmitate, mixed tocopherols, dimethylpolysiloxane, lecithin and sesame oils were used as additives. To determine the real impacts of additives, a quarter-fraction factorial experimental design with two levels and five factors was used. The changes in TPC and PTAG data were carefully evaluated during 10 h of frying at 170 ± 5 C with normal distribution (ND) graphs and analyzed using a one-way analysis of variance (ANOVA), followed by Tukey's Post-hoc test (α = 0.05). The results indicated that the increasing values for TPC and PTAG during the frying processes for all blends, TPC and PTAG contents reached maximum levels of 16.37 and 6.01 % respectively, which are below the limit values stated by official authorities for the quality assessment of frying oils. The ANOVA test results were in good agreement with ND graphs and data indicated that the impact of mixed tocopherols was significant for TPC formation, meanwhile the impact of lecithin and ascorbic palmitate × dimethylpolysiloxane were significant for PTAG formation. Thus, the present study should be considered to be a very useful guide for developing new frying oil formulations based on CSO by using food additives. © 2013 AOCS.