Biosafety laboratories are specialized in handling dangerous microorganisms, but there are cases where contaminants are leaked due to improper handling and other reasons. Therefore, an in-depth understanding of the pattern of infection after a laboratory spill can help laboratory personnel get out of danger as soon as possible and avoid the occurrence of infection events. In this paper, we take the COVID-19 virus outbreak in recent years as an example to explore the probability of infection of laboratory personnel under different circumstances. The study used computational fluid dynamics (CFD) to predict the change of contaminant concentration over time in a typical laboratory, and then analyzed the relationship between contaminant concentration and infection probability by using a metrological response model, and calculated the infection probability of indoor personnel over time in the presence or absence of obstacles in the laboratory and the different locations of contaminant leakage, respectively. The results showed that the probability of personnel infection remained basically stable after 8 min of contaminant leakage; at the same time, the probability of infection was higher when the contaminant source was located below the exhaust vent than in other locations; and the probability of illness was lower in laboratories with obstacles than in laboratories without obstacles under the same conditions. This finding is helpful for laboratory layout design.