T-cells orchestrate the inflammatory responses in atherosclerosis, and their function is modified by the lipoprotein milieu and complement activity. We investigated the effects of fluvastatin on the expression of complement decay-accelerating factor (DAF/CD55) antigen, and the levels of transcription factors in circulating T-cells in hypercholesterolemia. The hypercholesterolemic state was associated with the upregulation of DAF expression on circulating T-cells and increased levels nuclear factor kappa B (NF-kB) and interferon regulatory factor 4 (IRF4). Notably, the elevated levels of DAF and NF-kB expression persisted following treatment with fluvastatin. Therefore, the pleiotropic effects of fluvastatin are partially ascribed to its ability to mediate T-cell activation and regulate complement activity. Consequently, enhanced therapeutic interventions that targets complement-induced T-cell activation may be important in mitigating the development of atherosclerosis and major cardiovascular events in individuals with hypercholesterolemia.