The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019 has spread globally, causing a pandemic of respiratory illness. The virus primarily affects the lungs, where it induces respiratory distress syndrome ranging from mild to acute. However, a growing body of evidence shows COVID-19 pathology in other organs that also carry the ACE-2 receptor, including the placenta. Most newborns delivered from COVID-19 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. In this study, we compared a unique collection of placental tissue samples from COVID-19 positive and gestational age-matched non-COVID-19 samples. Using AKOYA’s ultrahigh-plex Phenocycler assay, we mapped dozens of protein biomarkers in situ with single-cell and subcellular spatial resolution to produce unbiased and comprehensive spatial biomarker maps of potential placental pathobiology associated with COVID-19 infections. Our antibody panel was aimed at in-depth identification of immune cell lineages, activation states, immune checkpoints, and tissue structures; infected cells were identified via the deployment of two antibodies directed at COVID-19 spike and capsid proteins, as well as an antibody directed against the ACE-2 receptor. All imaging data were obtained at single-cell resolution across whole tissue samples, and cellular phenotypes were subsequently identified via unsupervised clustering methods. These data are the first of their kind and will provide additional insight into the pathobiology of COVID-19.