INTRODUCTION: Inflammation plays a key role in the development of insulin resistance and atherosclerosis. Fatty acids and fiber intake can selectively alter gene expression by modifying inflammation. PURPOSE: We compared the postprandial expression of inflammatory genes after 2 distinct high-fat breakfast meals, before and after 1-month dietary interventions. METHODS: This crossover clinical trial included 18 individuals at low-to-moderate cardiometabolic risk participating in evaluations before and after two 4-week breakfast interventions-one rich in saturated fatty acids (SFA) and the other in unsaturated fatty acids (unSFA) and fiber. Participants underwent meal tests with similar compositions to the breakfasts. Variables were compared by Student t test. The expression of inflammatory genes in leukocytes was analyzed using RT-PCR. RESULTS: Before and after the intervention with the SFA-enriched breakfast, this meal test induced a higher relative postprandial IL-1ß expression compared to the responses to the unSFA and fiber-enriched meal (p = 0.02). On the other hand, following the intervention with the unSFA-fiber-enriched breakfast, postprandial IL-6 expression showed a reduction tendency comparing to the pre-intervention value (p = 0.08). Although fasting IL-1ß, IL-6, MCP-1 and IFN-γ expressions had not changed after interventions, their circulating levels increased after the SFA-enriched meal test but not after the unSFA meal (p value between changes < 0.05). CONCLUSIONS: Our findings indicated that a single SFA-enriched meal is able to acutely induce the IL-1ß expression and regularly consumed could trigger systemic inflammation, while increased unSFA consumption could attenuate the inflammatory status. Further investigations are needed to deepen understanding how dietary fatty acids and fiber influence cardiometabolic risk profile by modulating inflammatory gene expression and circulating biomarkers. CLINICAL TRIAL INFORMATION: This study is registered at the Brazilian Registry of Clinical Trials (ReBEC ID: RBR-98x6b5). Available at: http://www.ensaiosclinicos.gov.br .