To identify a biological preservative that can protect beer from microbial contamination, which often results in the production of turbidity and off-flavor. The antimicrobial activity of a chitooligosaccharide against beer-spoilage bacteria and its effect on the fermentation performance of brewer's yeast was studied. Chitooligosaccharide with an average 2 kDa molecular weight was the best at inhibiting all tested beer-spoilage bacteria. The application of chitooligosaccharide in the brewing process did not influence the fermentation of brewer's yeast. The change in beer performance induced by the contamination of Lactobacillus brevis could be effectively controlled by application of chitooligosaccharide in the beer brewing process. The experimental data suggested that chitooligosaccharide should be an excellent preservative to inhibit beer-spoilage bacteria in the brewing process and in the end product.