OBJECTIVES: Fever is one of the most common symptoms in children. However, although the frequency of fever as the main symptom is high, there is considerable controversy in the management of children that have fever without source(FWS). The aim of this study was to determine the incremental rate of cost-effectiveness(CE) of presepsin compared with C–reactive protein(CRP) and procalcitonin in detecting severe bacterial infection(SBI) in children aged 29days to 36months with FWS according to pre-test probability in Colombia. METHODS: An economic analysis of cost-effectiveness structured using the technique of decision analysis(TreeAge Pro®) was performed. Systematic reviews and meta-analysis were analyzed to establish the sensibility and specificity of CRP, procalcitonin and presepsin, a consensus of experts determined the length of hospitalization, costs of hospitalization and tests evaluated were determined from the average direct costs(USD). The cutoffs used were < 0.5 mg/dl for procalcitonin, > 40 mg/L for CRP and 625 pg/ml for Presepsin. The pre-test probability ranged from 10%-90%, considering low, intermediate and high probability of SBI. RESULTS: The different strategies had similar cost-effectiveness for a correctly diagnosed patient with SBI, mainly in the pre-test probability range of 10% - 50%, in which CPR was the most C/E. Presepsin was the most C/E strategy for the pretest probability scenarios between 60%-90% and procalcitonin was dominated throughout all probabilities. Effectiveness for presepsin was the highest in all scenarios, 82%-92%. CONCLUSIONS:  In the clinical practice, a large amount of children with FWS have a wide range of pre-test probabilities of SBI. Pre-test probability ranges from 3%-30%, our results found that CRP can be a good diagnostic tool in Colombia for pediatric patients with a 50% or less pre-test probability of SBI. Taking into consideration the greater effectiveness of Presepsin in all scenarios, would its cost be lowered, the same C/E may be achieved.