Inflammation may play a role in the link between high salt intake and its deleterious consequences. However, it is unknown whether salt can induce proinflammatory priming of monocytes and macrophages in humans. We investigated the effects of salt on monocytes and macrophages in vitro and in vivo by performing a randomized crossover trial in which 11 healthy human subjects adhered to a 2-week low-salt and high-salt diet. We demonstrate that salt increases monocyte expression of CCR2, a chemokine receptor that mediates monocyte infiltration in inflammatory diseases. In line with this, we show a salt-induced increase of plasma MCP-1, transendothelial migration of monocytes, and skin macrophage density after high-salt diet. Macrophages demonstrate signs of an increased proinflammatory phenotype after salt exposure, as represented by boosted LPS-induced cytokine secretion of IL-6, TNF, and IL-10 in vitro, and by increased HLA-DR expression and decreased CD206 expression on skin macrophages after high-salt diet. Taken together, our data open up the possibility for inflammatory monocyte and macrophage responses as potential contributors to the deleterious effects of high salt intake.