Pseudo-albinism is a complex condition, caused by a multitude of factors and negatively affecting flatfish aquaculture. The majority of studies focused on alterations in pigmentation, the most notable change in these animals. In this study, we investigated if pseudo-albinism in Solea senegalensis (Senegalese sole) could modify the microbiomes of two important innate immune barriers, the skin and intestine. The microbiome (16S rRNA analysis) was highly diverse in pigmented and pseudo-albino skin while the gut microbiome had low complexity and diverged between the two pigmentation phenotypes. The study reveals that pseudo-albinism in addition to pigmentation changes is associated with a modification in the gut microbiome.