Objectives To assess the effect of 1‐week high salt (HS) diet on the role of cyclooxygenases (COX‐1,‐2) and vasoconstrictor prostaglandins ‐ thromboxane A2 (TXA2) and prostaglandin F2α (PGF2α) on skin microcirculatory blood flow and to detect its effect on markers of endothelial activation such a soluble cell adhesion molecules (sCAMs). Methods Young women (N = 54) were assigned to either HS diet group (N = 30) (∼14 g of NaCl/day) or low salt (LS) diet group (N = 24) (<2.3 g NaCl/day) for 7 days. Post‐occlusive reactive hyperemia (PORH) in the skin microcirculation was assessed by laser Doppler flowmetry (LDF). Plasma Renin Activity (PRA), plasma aldosterone, plasma and 24 h‐urine sodium and potassium, plasma concentrations of TXB2 (stable TXA2 metabolite) and PGF2α, sCAMs and blood pressure (BP) were measured before and after diet protocols. One HS diet group subset received 100 mg of indomethacin (non‐selective COX‐1,2 inhibitor), and another HS group subset received 200 mg of celecoxib (selective COX‐2 inhibitor) before repeating LDF measurements. Results BP was unchanged after HS diet, but significantly reduced after LS diet. 24 h‐urinary sodium was increased, PRA and plasma aldosterone levels decreased after HS diet. HS diet significantly impaired PORH and increased TXA2, but did not change PGF2α levels. Indomethacin restored microcirculatory blood flow, reduced TXA2. In contrast, celecoxib decreased TXA2 levels, but had no significant effects on blood flow. Conclusions Restoration of of PORH by indomethacin during high salt diet suggest an important role of COX‐1 derived vasoconstrictor metabolites in regulation of microvascular blood flow during high salt intake. This article is protected by copyright. All rights reserved