Diagnosis of invasive fungal disease (IFD) in patients under intensive care is challenging. Circulating biomarkers, (1,3)-β-D-glucan (BG) and galactomannan (GM), were prospectively assessed in 98 critically ill patients at risk of IFD. There were 11 cases of invasive aspergillosis (IA; 4 proven and 7 probable), 9 cases of proven invasive candidiasis (IC), 1 case of mixed proven IC and probable IA, 1 case of proven zygomycosis, and 1 case of mixed mycelial proven IFD. In all IA cases there was no significant difference when the area under the receiver operating characteristic curve (AUC) of GM (0.873 [95% CI, 0.75-0.99]) and BG (0.856 [95% CI, 0.71-0.99]) were compared (p=0.871). The AUC for BG in IC and for the rest of the IFD cases was 0.605 (95% CI, 0.39-0.82) and 0.768 (95% CI, 0.63-0.90) respectively. Positive BG (40%) predated blood culture (n=3) and abdominal pus (n=1) a mean of 3.25 days before Candida was grown. In patients with IFD caused by molds, BG appeared a mean of 5.65 days before culture results. For the diagnosis of patients at risk of IC, BG has shown a high NPV (94.5%), with positive results also predating blood cultures in 30% of patients. In conclusion, early BG results permit a timely initiation of antifungal therapy in patients at risk of IFD. © 2011 Springer-Verlag.