Objective To analyze the protective effect of esmolol combined with early goal-directed therapy on myocardial function in patients with severe sepsis. Methods The clinical data of patients with severe sepsis who were treated in our hospital were retrospectively analyzed. According to the principles of randomization, balance and control, 30 cases receiving esmolol combined with early goal-directed therapy were selected as the observation group. The other 30 cases who were given early goal-directed therapy during the same period were selected as the control group. The effects of the two treatment regimens on the levels of hemodynamic indices, cTnT, BNP, TNF-a, IL-1β, Lac, central venous oxygen saturation(ScvO2) and other indices were compared, and 28-day survival rate was statistically analyzed. Results After treatment, Ea/Aa in the observation group was increased significantly, and HRwas decreased significantly. Only HRwas decreased significantly in the control group. There was no statistically significant difference within groups and between the two groups in other hemodynamic indices (P＞0. 05); the levels of cTnT, BNP, TNF-a, and IL-1β in both groups were significantly decreased and the observation group was lower than the control group. The differences within groups and between groups were statistically significant; the serum Lac was decreased and ScvO2 was increased in both groups. The serum Lac in the observation group was lower than that in the control group, and ScvO2 was higher than that in the control group. There were statistically significant differences within groups and between groups (P＜0. 05); the survival rate in the observation group was slightly higher than that in the control group, but the difference was not statistically significant(χ2=0. 480, P=0. 488). Conclusion Esmolol combined with early goal-directed therapy may benefit myocardial protection in patients with severe sepsis.