The aim of this study was to investigate if food could reduce pain perception in a group of 16 healthy human volunteers (8 male and 8 female), and to explore the differential effects of macronutrient composition on the response to cold-induced pain. All subjects underwent the cold pressor test (CPT) on 3 occasions in a counterbalanced order, before and after administration of isoenergetic high-fat low-carbohydrate (CHO) and high-CHO low-fat meals, and when no meal was given. The CPT was carried out 4 times on each test day, once before the meal, and 0.5, 1.5, and 2.5 h after the meal, and at the equivalent times on the day when no food was given. Radial pulse and blood pressure measurements and visual analogue scales of mood/emotional state were carried out before and after each CPT. Mean pain scores were significantly reduced following both meals compared with the no-food condition. The maximum reduction in pain occurred 1.5 h after ingestion, and a significantly greater effect was exerted by the high-fat low-CHO meal compared with the high-CHO low-fat meal. These results demonstrate that food, particularly when rich in fat, significantly reduces the pain induced by the cold pressor stimulus in healthy human subjects.