Many foods are prepared by deep-frying as this provides unique flavors/textures that improve overall palatability to consumers. Sunflower oil is one of the most widely-used frying oils in the world. However, during frying, fats in the foodstuff are heated to > 150° C and concurrently come into contact with agents found in the air, water, and other foods being cooked at the same time. Since long-term consumption of oxidized/oxidation products can contribute to the development of a variety of pathologies. Used cooking oil has become of increased concern to both health administrators and consumers. Few studies have sought to examine potential immunomodulatory effects from exposures to sunflower oil or its oxidized/oxidation products. To address this gap in knowledge, here, sunflower oil was used to fry potatoes at 190° C, every 30 min; a new 100 g batch of slices was cooked. Frying was performed continuously for 5h/day for 2 and 4 days (10 and 20 h total), and then the parental uncooked oil and each of the used oils were provided to Wistar rats in their diet (at 20% level) for a total of 10 weeks. Measures of body weight\food intake indicated that diets containing the used oils led to slightly reduced food intakes and host weights. Kidney weights were not affected by consumption of the two used oils, but the liver was enlarged in rats fed with the oil treated for 20 h. Evaluation of key lipid-serum parameters, i.e., total cholesterol, HDL cholesterol, and triglycerides, revealed a diet-related decrease in each; oxidized fats reduce their concentration compared to fresh fats. Conversely, serum LDL cholesterol levels were increased. Histological analyses indicated that consumption of the oxidized oils caused both kidney (e.g., tubular/glomerular dilation, vascular congestion, inflammation, tubular necrosis) and liver (e.g., vascular congestion, inflammation, necrosis) damages. Assessments of host immune function, i.e., ability to form antibody to ovalbumin (OVA) challenge, indicated that in rats fed the used oil, there were significant decreases in serum anti-OVA antibody levels. This suggested that host immunocompetence could be compromised as a result of long-term consumption of a diet containing a relatively high (i.e., 20%) content of used sunflower oils.