In summary, we demonstrated that the presence of the 6 g spice blend in a HFCM significantly reduced postprandial IL-1β, IL-6, and IL-8 secretion from LPS-stimulated PBMCs in men with overweight/obesity at risk of CVD, suggesting a potential anti-inflammatory effect of spices. Here, IL6 is linked to obesity due to melanocortin 4 receptor deficiency.