Objective: We examined the effects of commercially available unsaturated fat dietary supplements on blood lipids, and on markers of malnutrition and inflammation, in an adult population of hemodialysis (HD) patients. Design: This was a restricted, randomized (equal blocks), investigator-blinded 2 × 6 week crossover trial, without a washout interval. Setting: This study was conducted at the Department of Nephrology, Copenhagen University Hospital Herlev, Herlev, Denmark, in spring 2007. Patients: Participants included 40 (30 males and 10 females) stable, adult patients undergoing regular HD, with a mean age of 64.6 years and a mean body mass index of 23.3 kg/m2. Intervention: In addition to patients' habitual diets, oral unsaturated fat supplements (90 mL of Calogen [SHS International, Ltd., Liverpool, UK] and 4 capsules of Pikasol [Dansk Droge, Ishoej, Denmark]) were given in one period, whereas no supplements were given in the other. Dietary supplements contributed 1.8 MJ (430 kcal), 47 g fat, 26.5 g monounsaturated fatty acids, and 3 g marine n-3 polyunsaturated fatty acids per day. Blood sampling and nutritional assessments were performed at baseline, after 6 weeks, and after 12 weeks. Main Outcome Measures: Dietary intakes, blood lipids, dry body weight, serum albumin, and serum C-reactive protein comprised our main outcome measures. Results: According to a per-protocol analysis of 14 study completers, fat supplementation resulted in significantly increased total energy intake (+1.6 MJ/day, or 380 kcal/day) and an increased dietary fat energy percentage (+9%). We observed no significant changes in blood lipids. Dry body weight (+0.49 kg, P = .04) increased, and serum C-reactive protein concentration fell (-1.69 mg/L, P = .01), with fat supplementation. Intention-to-treat analysis of 39 participants confirmed the absence of adverse blood-lipid changes. Conclusions: Unsaturated fat supplementation increased total dietary energy intake to recommended levels, had no adverse impact on blood lipids, improved nutritional status as assessed according to dry body weight, and reduced systemic inflammation as assessed according to C-reactive protein serum concentrations. Adding unsaturated fat to the diet seems to be a safe and effective way to prevent and treat malnutrition in hemodialysis patients.