The present study aimed to assess the effect of a 1‐week high‐salt (HS) diet on the role of cyclo‐oxygenases (COX‐1 and COX‐2) and the vasoconstrictor prostaglandins, thromboxane A₂ (TXA₂) and prostaglandin F_2α (PGF_2α), on skin microcirculatory blood flow, as well as to detect its effect on markers of endothelial activation such as soluble cell adhesion molecules. Young women (n = 54) were assigned to either the HS diet group (N = 30) (∼14 g day^–1 NaCl ) or low‐salt (LS) diet group (N = 24) (<2.3 g day^–1 NaCl ) for 7 days. Post‐occlusive reactive hyperaemia (PORH) in the skin microcirculation was assessed by laser Doppler flowmetry. Plasma renin activity, plasma aldosterone, plasma and 24 h urine sodium and potassium, plasma concentrations of TXB₂ (stable TXA₂ metabolite) and PGF_2α, soluble cell adhesion molecules and blood pressure were measured before and after the diet protocols. One HS diet group subset received 100 mg of indomethacin (non‐selective COX‐1 and COX‐2 inhibitor), and another HS group subset received 200 mg of celecoxib (selective COX‐2 inhibitor) before repeating laser Doppler flowmetry measurements. Blood pressure was unchanged after the HS diet, although it significantly reduced after the LS diet. Twenty‐four hour urinary sodium was increased, and plasma renin activity and plasma aldosterone levels were decreased after the HS diet. The HS diet significantly impaired PORH and increased TXA₂ but did not change PGF_2α levels. Indomethacin restored microcirculatory blood flow and reduced TXA₂. By contrast, celecoxib decreased TXA₂ levels but had no significant effects on blood flow. Restoration of of PORH by indomethacin during a HS diet suggests an important role of COX‐1 derived vasoconstrictor metabolites in the regulation of microvascular blood flow during HS intake.