We identified that alterations to Ly6Chigh monocyte phenotype during obesity are TNF‐dependent, begin in the bone marrow, and lead to a higher prevalence of circulating immature and migration‐primed inflammatory Ly6Chigh monocytes that positively correlate with serum insulin, linking peripheral immune function with endocrine dysregulation. Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.