Traditional risk factors are not adequate for predicting serious bacterial infection (SBI) in febrile infants. The purpose of this study was to evaluate the diagnostic value of the plasma level of soluble form of triggering receptor expressed on myeloid cells-1 (sTREM-1) in predicting SBI in febrile infants less than 3 months old. Forty-four febrile infants less than 3 months old with clinical suspicion of SBI were enrolled. Blood was drawn for measurement of plasma sTREM-1 levels, and microbiological cultures were obtained at the time of admission. Twenty-three infants (52.3%) had SBI and 21 infants (47.7%) had no evidence of SBI based on the results of bacterial culture. sTREM-1 levels were significantly higher in infants with SBI than in infants without SBI (mean+/-SD, 324.6+/-546.3 versus 7.7+/-16.4, P<0.0001 after adjusting for age). The area under the receiver-operating characteristic curve was 0.88 for the sTREM-1 level. At a cutoff level of 24.4 ng/mL, the sTREM-1 level yielded a sensitivity of 87%, a specificity of 81%, a positive likelihood ratio of 4.6, and a negative likelihood ratio of 0.2 for differentiating between presence and absence of SBI. In conclusion, sTREM-1 may become a valuable diagnostic tool in the initial evaluation of febrile young infants.