Three bisbenzylisoqinoline alkaloids, chondocurine (Chon), berbamine (Ber), and cycleanine (Cyc) were tested for their protective effect on the quick death of mice primed with bacillus Calmette Guerin (BCG) and elicited with lipopolysaccharide (LPS). Seven-consecutive treatments with Chon or Cyc at a dose of 10 mg/kg following BCG priming resulted in significant improvement in the survival rate. A single dose of Chon also protected the BCG/LPS-treated mice from death if it was given immediately after, not 4 h after, LPS elicitation. These data show that bisbenzylisoquinoline alkaloids can protect mice from the lethal toxicity induced by the BCG/LPS combination treatment by inhibiting the priming with BCG or the elicitation with LPS.