Background <p>An abnormal perioperative blood lactate level has been reported to be associated with poor outcomes after cardiac surgery. However, their impact on female patients remains underexplored. This large-scale retrospective study evaluated the relationship between serum lactate level and one-year mortality in critically ill female patients with coronary artery bypass grafting.</p> Methods <p>We conducted a retrospective cohort analysis using data from an American ICU registry, focusing on female patients admitted for CABG at Beth Israel Deaconess Medical Center from 2008 to 2023. The primary outcome was one-year mortality. We employed Cox regression and a restricted cubic spline to examine the association between serum lactate and outcomes.</p> Results <p>A total of 1,279 female adult patients were included, with a mean age of 70.8 ± 10.0 years and a mean BMI of 30.8 ± 6.9&#xa0;kg/m². After adjusting for confounders, Cox regression revealed that patients in the lowest quartile (Q1: &lt;1.75 mmol/L) had a 0.96-fold increased risk of one-year mortality (HR 1.96; 95% CI 1.05–3.67, <i>P</i> = 0.036), while those in the third quartile (Q3: &gt;2.3 mmol/L) had a 1.2-fold increased risk (HR 2.2; 95% CI 1.19–4.07, <i>P</i> = 0.012), compared to the second quartile (Q2: 1.75–2.3 mmol/L). Spline regression indicated a U-shaped dose-response relationship, with the lowest mortality risk observed at a serum lactate level of 140.5 mmol/L. Stratified and sensitivity analyses supported these findings.</p> Conclusions <p>Our study suggests a U-shaped relationship between serum lactate levels and one-year mortality in female CABG patients.</p>