Background The optimal timing for initiating norepinephrine in septic shock is debated. This updated systematic review and meta-analysis aimed to evaluate the impact of early versus delayed norepinephrine initiation on mortality and clinical outcomes in adults with septic shock. Methods A systematic search in Pubmed, EMbase and the Cochrane Library to identify eligible randomized controlled trials, propensity score matching (PSM) and observational studies that compare early norepinephrine initiation with non-early norepinephrine initiation in patients with acute circulatory failure. The primary outcome was mortality in intensive care unit. Secondary outcomes included intensive care unit length of stay, fluid volume received at 6 h, norepinephrine dose, mechanical ventilation-free days, renal replacement therapy free days, and time to achieve a targeted mean arterial pressure (MAP). Meta-analysis and subgroup analysis were conducted to calculate odds ratio (OR) or mean difference with 9