Lethrinus mahsena, a species found throughout tropical and subtropical marine settings, is important to coastal ecosystems and has a high economic value. The impact of parasite infestations on these fish populations is widely recognized, but the precise histopathological responses to infestations requires further studies. This investigation aimed to investigate the histopathological changes in the intestines of Lethrinus mahsena caused by Anisakis simplex larvae. Over a year, 234 Lethrinus mahsena samples were monthly collected at the Rass Mehsen site on Saudi Arabia's Jeddah coast. The intestines of the examined fish were carefully checked for parasitic infestations. Based on the histopathological investigations of fish, considerable changes were recorded in the intestine. The mucosal layer was detected with the most obvious alterations, evidenced by significant desquamation and morphological abnormalities. The intestinal epithelium's structural integrity was disrupted, resulting in the loss of intestinal villi and the creation of inflammatory infiltrations. These findings reveal the severe impact of helminth nematodes infestations on the gut morphology of Lethrinus mahsena, emphasizing the importance of additional investigation into the mechanism driving these pathological changes.