Obesity is associated with hyperlipidemia, electrical remodeling of the heart, and increased risk of supraventricular arrhythmias in both male and female patients. The delayed rectifier K+ current (I-K), is an important regulator of atrial repolarization. There is a paucity of studies on the functional role of I-K in response to obesity. Here, we assessed the obesity-mediated functional modulation of I-K in low-fat diet (LFD), and high-fat diet (HFD) fed adult guinea pigs. Guinea pigs were randomly divided into control and obese groups fed, ad libitum, with a LFD (10 kcal% fat) or a HFD (45 kcal% fat) respectively. Action potential duration (APD), and I-K were studied in atrial myocytes and I-Kr and I-Ks in HEK293 cells using whole cell patch clamp electrophysiology. HFD guinea pigs displayed a significant increase in body weight, total cholesterol and total triglycerides within 50 days. Atrial APD at 30% (APD(30)) and 90% (APD(90)) repolarization were shorter, while atrial I-K density was significantly increased in HFD guinea pigs. Exposure to palmitic acid (PA) increased heterologously expressed I-Kr and I-Ks densities, while oleic acid (OA), severely reduced I-Kr and had no effect on I-Ks. The data are first to show that in obese guinea pigs abbreviated APD is due to increased I-K density likely through elevations of PA. Our findings may have crucial implications for targeted treatment options for obesity-related arrhythmias. Published by Elsevier Inc.