In order to examine the effect of BLP tolerance on cardiac dysfunction in CLP-induced septic mice, cardiac function was measured via echocardiography at various time points following induction of sepsis by CLP in BLP-tolerant and control C57BL/6 mice. Levels of tumour necrosis factor α (TNF-α), interleukin 10 (IL-10) and Toll-like receptor 2 (TLR2)-myeloid differentiation factor 88 (MyD88)-dependent signaling molecules in the myocardium were also examined. Cardiac function was significantly decreased 6-12 h following CLP-induced sepsis compared with that of sham controls, with cardiac output decreasing from 0.50 ±0.06 ml/s to 0.16 ±0.04 ml/s at 6 h and 0.57 ±0.06 ml/s to 0.13 ±0.02 ml/s at 12 h, whereas BLP tolerance attenuated CLP-induced cardiac dysfunction at 12 h following CLP with cardiac output increasing from 0.13 ±0.02 ml/s to 0.26 ±0.05 ml/s at 12 h. TNF-α, IL-10 and TLR2-MyD88-dependent signaling molecules in the myocardium were not significantly different among BLP-tolerant or non-tolerant control groups. These findings suggest that low dose BLP pretreatment can attenuate cardiac dysfunction, increasing the survival rate of septic mice. This effect did not involve TNF-α, IL-10 or TLR2-MyD88-dependent cytokines. Bacterial lipoprotein pretreatment attenuated cardiac dysfunction in CLP sepsis. TNF-α, IL-10 and TLR2-MyD88-dependent signaling molecules did not contribute to cardiac dysfunction observed in CLP-induced sepsis.