The prevalence of obesity in industrialized societies has become markedly elevated. In contrast, model organism research shows that reducing caloric intake below ad libitum levels provides many health and longevity benefits. Despite these benefits, few people are willing and able to reduce caloric intake over prolonged periods. Prior research suggests that mannooligosaccharide (MOS or mannan) supplementation can increase lifespan of some livestock and in rodents can reduce visceral fat without reducing caloric intake. Hence, we tested the effect of MOS supplementation as a possible calorie restriction (CR) mimetic (CRM) in mice. C57Bl/6J male mice were fed a high-fat western type diet with or without 1% MOS (by weight) supplementation (n = 24/group) from 8 to 20 weeks of age. Animals were housed individually and provided 95% of ad libitum food intake throughout the study. Body weight was measured weekly and body composition (lean and fat mass) measured noninvasively every 3 weeks. Individual fat depot weights were acquired by dissection at study completion. Supplementation of a high-fat diet with 1% MOS tended to reduce total food intake (mean ±s.d.; control (CON): 293±69 10.53g, MOS: 288±10 11.82g; P = 0.09) during the study. Moreover, MOS supplementation had no significant effect on final body weight (CON: 25±21 2.31g, MOS: 25±28 1.49g; P = 0.91), total fat (CON: 4±72 0.90g, MOS: 4.82± 0.83g; P = 0.69), or visceral fat (CON: 1.048 0.276g, MOS: 1.004±0.247g; P = 0.57). Contrary to previous research, MOS supplementation had no discernable effect on body weight gain or composition during this 12-week study, challenging the potential use of MOS as a CRM or body composition enhancer. © 2010 The Obesity Society.