We hypothesized that lipopolysaccharide (LPS)-induced suppression of vasoreactivity is caused by increased vascular COX-2 and downstream activation of eNOS by PGE 2 in the vascular wall. To address this, chronic indwelling catheters were placed in the femoral artery and vein in mice for blood pressure measurement and infusion, respectively. Five days after surgery, blood pressure and heart rate were measured in conscious mice. The resting mean arterial pressure was 105.77.1 mmHg and heart rate 627.552.6 bpm. An LPS bolus (055:B5, 2 mg/kg, i.v.) reduced blood pressure significantly after 4h (82.97.9 vs. control) and after 6h blood pressure was 79.33.6 mmHg. Heart rate was significantly reduced 2 h after LPS (569.870.3) and after 6 h heart rate was 315.150.6 (n=11). Blood pressure and heart rate were not significantly different in COX-2 -/- mice (n=8) compared to wild type (+/+) mice after LPS (n=4). Aorta-rings from COX-2 (+/+) and (-/-) mice were incubated with LPS (055:B5, 50 g/mL, 18h, 37 °C) in cell culture medium and isometric tension was recorded with a myograph (2 × 10^-7 M Phenylephrine (PE), 1h). Absence of functional COX-2 in the vessels did not alter the effect of LPS on vasoreactivity in response to PE. We conclude that COX-2 is not critical for acute blood pressure decrease or depressed vascular function in murine models of LPS endotoxemia.