Pre-metabolic syndrome (pre-MetS) may represent the best transition phase to start treatments aimed at reducing cardiometabolic risk factors of MetS. In this study, we investigated the effects of the marine microalgaTisochrysis luteaF&M-M36 (T. lutea) on cardiometabolic components of pre-MetS and its underlying mechanisms. Rats were fed a standard (5% fat) or a high-fat diet (20% fat) supplemented or not with 5% ofT. luteaor fenofibrate (100 mg/Kg) for 3 months. Like fenofibrate,T. luteadecreased blood triglycerides (p< 0.01) and glucose levels (p< 0.01), increased fecal lipid excretion (p< 0.05) and adiponectin (p< 0.001) without affecting weight gain. Unlike fenofibrate,T. luteadid not increase liver weight and steatosis, reduced renal fat (p< 0.05), diastolic (p< 0.05) and mean arterial pressure (p< 0.05). In visceral adipose tissue (VAT),T. lutea, but not fenofibrate, increased the β3-adrenergic receptor (β3ADR) (p< 0.05) and Uncoupling protein 1 (UCP-1) (p< 0.001) while both induced glucagon-like peptide-1 receptor (GLP1R) protein expression (p< 0.001) and decreased interleukin (IL)-6 and IL-1β gene expression (p< 0.05). Pathway analysis on VAT whole-gene expression profiles showed thatT. luteaup-regulated energy-metabolism-related genes and down-regulated inflammatory and autophagy pathways. The multitarget activity ofT. luteasuggests that this microalga could be useful in mitigating risk factors of MetS.