In this systematic review, we critically evaluated human clinical trials that assessed the effects of dietary fat quality on metabolic endotoxaemia. The studies were selected from three databases (PubMed, Scopus and Cochrane Library), and the keywords were defined according to the Medical Subject Headings indexing terminology. Two authors searched independently, according to the pre-defined selection criteria. Quality and risk assessment of bias for each selected study were also evaluated. The results of the included studies demonstrated associations between higher SFA intake and increased postprandial lipopolysaccharide (LPS) concentrations. On the other hand, after the consumption of PUFA, bloodstream LPS concentrations were lower. However, in none of the long-term studies, the consumption of dietary fats did not seem to exert effects on LPS concentration. Hence, SFA seem to act as a risk factor for transient increase in endotoxaemia, while PUFA demonstrated exerting a protective effect. Taken together, the evidence suggests that the dietary fatty acid profile may influence bloodstream endotoxin concentrations through modulation of factors such LPS clearance, alkaline phosphatase activity, bile acid metabolism, intestinal permeability and intestinal microbiota composition.