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Omega-3 fatty acids reduce triglycerides and have several positive effects on different organs and systems. They are also found in the plasma membrane in variable amounts in relation to genetics and diet. However, it is still unclear whether omega-3 supplementation can reduce the occurrence of major cardiovascular events (MACEs). Two trials, REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), with highly purified EPA, and STRENGTH (Effect of High-Dose Omega-3 Fatty Acids vs. Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk), with a combination of EPA and DHA, have produced different outcomes, triggering a scientific debate on possible explanations for the discrepancies. Furthermore, doubts have arisen as to the anti-inflammatory and anti-aggregating activity of these compounds. Recent studies have, however, highlighted interesting effects of EPA and DHA on erythrocyte membrane fluidity (EMF). EMF is governed by a complex and dynamic biochemical framework, with fatty acids playing a central role. Furthermore, it can be easily measured in erythrocytes from a blood sample using fluorescent probes. Recent research has also shown that EMF could act as a possible cardiovascular risk factor biomarker. This review aims to synthetize the latest evidence on erythrocyte membrane fluidity, exploring its potential role as a biomarker of residual cardiovascular risk and discussing its clinical relevance. Further, we aim to dissect the possible biological mechanisms that link omega-3 modifiable membrane fluidity to cardiovascular health. [ABSTRACT FROM AUTHOR]