AbstractVirus transmission is affected by population density, social distancing, and vaccination. This has been simulated only by mathematical models. Here, we report the first experimental model to mimic herd immunity to a human coronavirus using a microfluidic device filled with host cells. The device consists of 444 microchambers filled with susceptible (S0), infected (I0), and unsusceptible (U0) cells at specific ratios. The transmission rate and reproduction numbers were directly proportional to S0 and I0 and inversely proportional to U0. Herd immunity was achieved when the proportion of U0 was at 80% in a fixed number of uninfected (S0+U0) cells. These results were consistent with those from a mathematical model. The device can be used for predicting virus transmission.One-Sentence SummaryWe present the first experimental model enabling the simulation of herd immunity in a microfluidic device filled with host cells to human coronavirus.