Baff is a critical mediator of B-cell survival that, if present in excess, fosters humoral autoimmunity. Although, Baff prevents deletion of self-reactive B-cells, its role in the regulation of activated B-cells has not been studied. Since activated B-cells are mainly controlled by Fas-mediated cell death, the aim of our work is to elucidate if Baff modulates this pathway. C57BL/6 mice splenic B-cells were cultured with medium, anti-m (5mg/ml), anti-CD40 (7.5mg/ml) or LPS (10mg/ml) in presence or absence of Baff (30ng/ml). Baff upregulates two key inhibitors of Fas-induced cell death, cIAP2 and cFLIP and decreases caspase-9 and -3 cleavage. However, Baff does not protect activated B-cells from Fas-mediated apoptosis and, even enhances Fas-killing of LPS-stimulated B-cells, as determined by studying the percentage of apoptosis in B-cells activated as described and cultured for extra 12h with anti-Fas or control Abs (apoptotic cells LPS+Baff:45% vs LPS:27%). Accordingly,  Baff greatly upregulates Fas expression only in LPS-activated B-cells (MFI LPS+Baff:179 vs LPS:135). This effect seems exclusive for TLR4-activated B-cells since, Baff does not upregulate Fas in CpG or poly(I:C)-activated B-cells. Interestingly, LPS and Baff have additive effects in the activation of PI3K/Akt pathway that has been shown, in other cell types, to up-regulate Fas expression. Our results suggest that Baff does not avoid activated B-cell control and indeed, depending on the activator, it turns B-cells more susceptible to Fas-killing.