B and T lymphocyte attenuator expression contributed to increased lymphoid organ cellular apoptosis following cecal ligation and puncture. Lymphoid cell apoptosis is observed during sepsis and is thought to contribute to infection susceptibility; we therefore evaluated the role of B and T lymphocyte attenuator (BTLA) in this process. Following cecal ligation and puncture (CLP) (24 hours), the wild-type (WT) mice (n = 10) were observed to have significantly increased thymic (A, B) and splenic (C, D) cell apoptosis via increased terminal deoxynucleotidyl transferase (TUNEL) staining (A, C) and nuclear condensation (hematoxylin and eosin staining) (B, D) when compared with sham mice (n = 6). Significantly lower apoptosis levels were observed in the BTLA-/- mice 24 hours post CLP (n = 10) compared with the sham mice (n = 3) (A to D). Similarly, 24 hours following CLP, the BTLA-/- mice had significantly lower thymic and splenic cell apoptosis levels compared with the observed WT CLP mice (A to D). Data are mean ± standard error of the mean. *P <0.05 using the Bonferroni post test following one-way analysis of variants. At least three fields per organ per sample at 20× magnification were used for the TUNEL staining quantification.