Aim: To describe and compare early with late vasopressor commencement in emergency department (ED) patients with sepsis and hypotension. Methods: This is a sub-study of the ARISE FLUIDS observational study conducted in 70 EDs in Australia and New Zealand. Adults with suspected sepsis and hypotension who received a vasopressor infusion in the first 24 h after ED presentation were included. ‘Early’ was defined as vasopressor commenced within 2 h from a) sepsis recognition, or b) triage. Results: 177 patients (mean age 68 years) received vasopressors and had a lactate of 3.0 (IQR 2.0–4.9) mmol/L and APACHE II score of 17.8 (SD 6.3). 110 (62%) received a single agent vasopressor with noradrenaline being the most common (n = 74) and 67 (38%) received multiple vasopressors, most commonly metaraminol then noradrenaline (20.3%, n = 36). One-third (34.7%, n = 62) had vasopressors started via a peripheral line. Vasopressors were started within 2 h of sepsis recognition in 74 patients and within 2 h of triage in 24 patients. Both early groups had a higher lactate (3.5 vs. 2.9mmol/L and 5.0 vs. 2.9mmol/L, both p <0.05) and received lower fluid volumes prior to vasopressor commencement (2.0 vs. 2.85 L and 1.55 vs. 2.4 L, both p <0.001), compared to patients receiving vasopressors later. No differences in duration of vasopressor infusion, need for organ support or in-hospital mortality were found. Conclusion: Early vasopressor commencement was associated with the administration of lower intravenous fluid volumes but not with duration of vasopressor use, organ support or mortality. Large prospective studies addressing this question are required.