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Fish epidermal mucus contains innate immune components, secreted by globlet cells that provide the primary defence against different pathogenic microbes and act as a barrier between fish and its immediate niche. The major function of mucus includes entrapment and sloughing of microbes. The mucus also contains many factors such as antimicrobial peptides (AMPs), lysozymes, lectins, proteases, etc that provide innate immunity. The AMPs secreted by epidermal mucus cells displayed antimicrobial activity against a variety of pathogens. Besides, mucosal lysozyme was found to produce significant bacteriolytic action whereas different proteases found in skin mucus of fish can kill the pathogens by cleaving its protein or by activating immunological mechanisms. Lectins are also mucosal agglutinins that play a diverse role in innate immunity like opsonization, activation of complement, etc. Epidermal mucus in fish thus provides an innate and fast acting protection which is non-specific and is found to be relatively temperature independent. The aim of the present review is to provide a broad overview of the different components of epidermal mucus including AMPs, proteases, lysozymes as well as their mode of action on pathogens.