Objective To evaluate  the short-term effects of  lamivudine  (LAM) and entecavir  (ETV)  therapy on chronic severe hepatitis B. Methods Total of 88 cases with chronic severe hepatitis B were analyzed,  retrospectively. The control group  (27 cases)  received conventional  therapy and  the  therapy groups were treated with LAM (35 cases) or ETV (26 cases) based on the comprehensive therapy. Results After 8 weeks therapy, the total bilirubin, international normalized ratio (INR) for prothrombin time and MELD score in the therapy groups were significantly  lower  than  those  in  the control group ( P ＜ 0.05). The  improvement rates and HBV DNA undetectable  in  the  therapy groups were significantly higher  ( P ＜ 0.05). According  to  the pretherapy MELD score, all patients were divided into two groups and the improvement rates in the therapy groups were higher than those in the control group when MELD score ≤ 25 ( P ＜ 0.05), while no significant differences were found when MELD score ＞ 25 ( P ＞ 0.05). No significant differences of short-term effects were found between lamivudine group and entecavir group. Conclusions LAM and ETV are both beneficial for chronic severe hepatitis B and should be used as early as possible.