Hubei hybrid wolfberry was used to study its nutritional quality and anti-fatigue effect and compare with that of the commercially available northern wolfberry as the raw material of the thick pulp beverage. The effects of Hubei hybrid wolfberry drink on relieving physical fatigue were investigated by analyzing its nutritional quality and determining the exhaustion time of swimming with a load in mice. In the animal experiments， the content of liver glycogen（LG），muscle glycogen （MG），blood lactic acid（BLA），blood urea nitrogen （BUN），malondialdehyde （MDA）， superoxide dismutase （SOD），and glutathione reductase （GR） after exercise in mice after gavage of Hubei hybrid wolfberry thick pulp beverage at different dosage（4，8，12 mL/kg） were determined and compared with that of the blank group. The results showed that active substances including phenolics 175.44 μg/g， flavonoids 98.91 μg/g， proteins 1.90 mg/g， betaine 0.30 mg/mL， and Se 1.59 μg/kg in Hubei hybrid wolfberry thick pulp beverage were higher than that of commercially available wolfberry thick pulp beverage， and had better antioxidant activity. The results of animal experiments showed that the medium-dosage and high-dosage group（daily gavage at 8 and 12 mL/kg） of Hubei hybrid wolfberry thick pulp beverage effectively prolonged the exhaustion time of swimming with a load in mice， and both of them significantly improved the anti-fatigue effect on mice （P<0.05）， 1.66 times and 2.10 times more than that in the blank group. The high-dosage group（daily gavage at 12 mL/kg） was 1.32 times higher than that of the commercially available commercially available wolfberry thick pulp beverage group， and the difference was significant（P<0.05）. After exercise， the content of MG and LG of mice in the high dosage group of Hubei hybrid wolfberry thick pulp beverage increased by 47.03% and 116.22% compared to the blank group， and the content of BLA， BUN， and MDA significantly decreased （P<0.05）， and the activity of SOD and GR significantly increased （P<0.05）， indicating that Hubei hybrid wolfberry thick pulp beverage has better anti-fatigue effect. It will provide a scientific basis for mining the health effect of Hubei hybrid wolfberry and a new idea for developing functional foods for people with exercise fatigue.