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Soybean meal (SBM) is one of the most commonly used vegetable ingredient to replace fish meal in fish diets. However, SBM is limiting in some essential amino acids and contains numerous antinutritional factors and antigens that can affect intestinal microbiota and innate immune system in several finfish species and crustaceans and compromise health. The impact of SBM on health and gut microbiota of aquatic animals is not only affected by SBM in general, but also on the degree of treatment of the meal and exposure. Recently, many studies are actively seeking ways to complement or balance those adverse responses induced by high inclusion of SBM in aquaculture diets. These include advanced processing and mixture of feed with other feed components to balance antinutritional factors. The impact of dietary soybean oil on gut microbiota has also been investigated but to a lesser extent than SBM. As the gastrointestinal tract has been suggested as one of the major routes of infection in finfish species and crustaceans, the effect of soybean products on the gut microbiota is important to investigate. Several studies have focus on supplementation of SBM on the adverse responses of the innate immune system as immunological mechanisms are likely involved in the underlying pathology. However, the precise cause of the inflammatory process has not yet been clarified, even though some investigations have suggested that alcohol-soluble antinutritional factors, especially soy saponins, are potential causative factors. Possible interactions between soybean products and innate immune system in several finfish species and crustaceans are discussed.