Objective: We intend to evaluate the prognostic value of serum albumin in children with Escherichia coli (E. coli) bloodstream infection (BSI). Methods: Retrospectively, 211 E. coli BSI children hospitalized at Children’s Hospital Affiliated Chongqing Medical University were enrolled. We applied logistic regression analyses to select the potential risk factors for mortality. And the Kaplan-Meier curve was plotted to compare mortality rates among different groups. Results: More than one six (17.54%, 37/211) of patients had hypoalbuminemia on admission and about ten percent (10.90%, 23/211) of patients with hypoalbuminemia secondary to the E. coli BSI. And nineteen (19/211, 9.00%) patients need invasive mechanical ventilation during hospitalization. The incidence of septic shock was 6.53% (18/211), and the mortality was 12.32% (26/211). Logistic regression analysis demonstrated that requiring for invasive mechanical ventilation, with secondary hypoalbuminemia after BSI, high pediatric risk of mortality (PRISM) III scores, and short time to positivity (TTP) were independently associated with mortality in children with E. coli BSI (Odds ratio [OR] 38.35, 95% Confidence interval [CI] 2.88-670.29, P =0.004; OR 7.72, 95% CI 1.02-62.10, P =0.044; OR 1.19, 95% CI 1.02-1.43, P =0.041; OR 0.72, 95% CI 0.55-0.88, P =0.005; respectively). Conclusions: Secondary hypoalbuminemia after E. coli BSI in children could independently predict the risk of mortality. Children with E. coli BSI who developed secondary hypoalbuminemia should be given more advanced therapy.