The predominant saturated fatty acids (SFA) in human diets are lauric acid (LA, C12:0), myristic acid (MA, C14:0), palmitic acid (PA, C16:0) and stearic acid (SA, C18:0). The aim of this study was to investigate whether diets containing individual SFA together with excess simple carbohydrates induce osteoarthritis (OA)-like changes in knee joints and signs of metabolic syndrome in rats. Rats were given either a corn starch diet or a diet composed of simple carbohydrates together with 20% LA, MA, PA, SA or beef tallow for 16 weeks. Rats fed beef tallow, SA, MA or PA diets developed signs of metabolic syndrome, and also exhibited cartilage degradation and subchondral bone changes similar to OA. In contrast, replacement of beef tallow with LA decreased signs of metabolic syndrome together with decreased cartilage degradation. Furthermore, PA and SA but not LA increased release of matrix sulphated proteoglycans in cultures of bovine cartilage explants or human chondrocytes. In conclusion, we have shown that longer-chain dietary SFA in rats induce both metabolic syndrome and OA-like knee changes. Thus, diets containing SFA are strongly relevant to the development or prevention of both OA and metabolic syndrome.