Neutrophil granulocytes (NGs) are among the key players in the defense againstAspergillus fumigatus(A. fumigatus). To better elucidate a pathophysiological understanding of their role and functions, we applied a human cell model using NGs from healthy participants and septic patients to evaluate their inhibitory effects on the growth ofA. fumigatusex vivo. Conidia ofA. fumigatus(ATCC®204305) were co-incubated with NGs from healthy volunteers or septic patients for 16 h.A. fumigatusgrowth was measured by XTT assays with a plate reader. The inhibitory effect of NGs on 18 healthy volunteers revealed great heterogeneity. Additionally, growth inhibition was significantly stronger in the afternoon than the morning, due to potentially different cortisol levels. It is particularly interesting that the inhibitory effect of NGs was reduced in patients with sepsis compared to healthy controls. In addition, the magnitude of the NG-driven defense againstA. fumigatuswas highly variable among healthy volunteers. Moreover, daytime and corresponding cortisol levels also seem to have a strong influence. Most interestingly, preliminary experiments with NGs from septic patients point to a strongly diminished granulocytic defense againstAspergillusspp.