Dietary fatty acid (FA) composition may influence metabolism, possibly affecting weight management. The purpose of this study was to compare the effects of a 5-d diet rich in PUFA v. MUFA. A total of fifteen normal-weight men participated in a randomised cross-over design with two feeding trials (3 d lead-in diet, pre-diet visit, 5-d PUFA- or MUFA-rich diet, post-diet visit). The 5-d diets (50 % fat) were rich in either PUFA (25 % of energy) or MUFA (25 % of energy). At pre- and post-diet visits, subjects consumed breakfast and lunch test meals, rich in the FA for that 5-d diet. Indirect calorimetry was used for 4 h after each meal. There were no treatment differences in fasting metabolism acutely or after the 5-d diet. For acute meal responses before diet, RER was higher for PUFA v. MUFA (0·86 (sem 0·01) v. 0·84 (sem 0·01), P<0·05), whereas diet-induced thermogenesis (DIT) was lower for PUFA v. MUFA (18·91 (SEM 1·46) v. 21·46 (SEM 1·34) kJ, P<0·05). After the 5-d diets, the change in RER was different for PUFA v. MUFA (−0·02 (sem 0·01) v. 0·00 (sem 0·01), P<0·05). Similarly, the change in fat oxidation was greater for PUFA v. MUFA (0·18 (sem 0·07) v. 0·04 (sem 0·06) g, P<0·05). In conclusion, acutely, a MUFA-rich meal results in lower RER and greater DIT. However, after a 5-d high-fat diet, the change in metabolic responses was greater in the PUFA diet, showing the metabolic adaptability of a PUFA-rich diet.