Ochratoxin A (OTA) is a nephrotoxin produced by many species in two fungal genera of Aspergillus and Penicillium under virtually all agricultural environments. Hence, OTA occurs frequently in agricultural commodities and their downstream products worldwide. In this study, thermal stability of OTA in the presence of sugars commonly added to food products including glucose, fructose, and sucrose was investigated by analyzing their reaction products with HPLC-FLD and LC-MS/MS. Samples were heated at three different temperatures (100, 125, and 150 °C) in 10-min intervals for up to 60 min in the absence of food matrix. Analysis showed increased OTα and OTα-amide and decreased OTA isomer (14-R-OTA) formation when OTA was heated with sugars. Among the sugars tested, adding fructose resulted in significantly lower OTA levels than glucose, sucrose, or no sugar added control. Addition of fructose also shifted OTA degradation product profile to less toxic OTα-amide, instead of OTA isomer which has similar toxicity to OTA. These results suggest that added sugars influenced the levels of OTA and its degradation products formed during thermal processing, and may provide a means to reduce the toxicity of OTA in food.