It has been reported that angiopoietin 2 (Ang-2) plays an integral role in the pathophysiology of sepsis and many other inflammatory diseases. However, the specific role of Ang-2 in septic shock has not been defined. The aim of the present study was to assess the predictive value of serum Ang-2 in patients with septic shock. Clinical data of 85 patients with septic shock and 10 healthy controls admitted to the intensive care unit with a diagnosis of septic shock were collected between January 2020 and October 2020 at Tongji Hospital (Wuhan, China). The serum levels of Ang-2 mRNA were quantified using a quantitative real-time PCR assay. Ang-2, SOFA and APACHE II scores were retrospectively analyzed in relation to 28-day mortality. The area under the receiver operating characteristic (ROC) curve (AUC) was used to discriminate the accuracy of the prediction. Mean Ang-2 mRNA levels in the patients with septic shock were significantly higher than those in the healthy controls (P<0.05), and the Ang-2 levels showed a downwards trend over time following treatment. The three indicators (AUCs, SEMs, P-values) were Ang-2 (0.82, 0.03, P<0.01), SOFA score (0.76, 0.04, P<0.01), and APACHE II score (0.73, 0.04, P<0.01). The present study confirmed that Ang-2 mRNA levels were significantly elevated in septic shock. The Ang-2 mRNA level at ICU admission in a patient with septic shock could be a predictive biomarker for mortality.