Objective: This study investigated the effects of chemically protected sodium butyrate (CSB) on growth performance, serum indicators, rumen fermentation parameters, and microbial communities in Gangba sheep.Methods: Twenty-four healthy 5-month-old male Gangba sheep with an initial body weight of 19.54±1.04 kg were randomly assigned to four groups and fed diets containing 0, 1.0, 5.0, and 10.0 g/kg CSB for 74 days. After a 14-day adaptation period, the daily feed intake of Gangba sheep was measured. Fecal samples were collected during the last 7 days of the trial, and serum and rumen fluid were sampled on the final day.Results: CSB improved final body weight, average daily dry matter intake, and average daily gain while reducing the feed conversion ratio of Gangba sheep (p<0.05). In addition, CSB improved the apparent digestibility of crude protein, dry matter, and neutral detergent fiber (p<0.05). Furthermore, CSB increased serum immunoglobulin G levels while decreasing tumor necrosis factor-α levels (p<0.05). Meanwhile, CSB increased serum growth hormone-releasing hormone levels (p<0.05). Furthermore, CSB increased rumen fluid pH and concentrations of ammonia nitrogen, acetic acid, iso-butyric acid, butyric acid, and total volatile fatty acids, as well as activities of lipase and butyrate kinase (p<0.05). Besides, CSB enhanced the rumen microbiota structure by increasing the relative abundance of Fibrobacter, unclassified Oscillospiraceae, and Ruminococcus.Conclusion: CSB improved immunological and hormone indicators, enhanced the rumen ecological environment, and increased feed digestibility and utilization, thereby promoting the growth of Gangba sheep. It is recommended to use a dosage of 5.0 g/kg dry matter for optimal growth performance and health benefits.