Toxoplasma gondii is an obligate intracellular parasite that is responsible for the human and animal disease toxoplasmosis. Toxoplasma belongs to the phylum Apicomplexa, which includes Plasmodium species (the agents of malaria) and Cryptosporidium spp. (responsible for severe diarrhea). All apicomplexan parasites undergo a unique form of motility to actively invade their target cell and create a vacuole to aid their intracellular survival. A better understanding of the host cell – parastite interaction during invasion will help to create new disease treatments. In this study, we used lattice light-sheet microscopy to capture whole cell volumes of T. gondii invasion using parasites expressing mCherry and the Ca2+ sensor GCaMP6. In addition, we applied a combination of live cell dyes and genetically encoded fluorescent reporters to label both membrane and cytoskeletal proteins in the host cell. Using this novel workflow, we are quantitatively investigating biophysical membrane changes and the reorganization of the cytoskeleton during host cell invasion by Toxoplasma. This study will reveal the role of the host cell during invasion of apicomplexan parasites and inform new therapies to treat diseases caused by this group of pathogens.