Interest in plant species that support pollinator health has been increasing in recent years. As a result, research into these historically overlooked species is increasing. One such taxon is milkweed (Asclepias spp.), a genus primarily native to North America that serves as an oviposition and food source for various pollinators, especially the monarch butterfly (Danaus plexippus L.). Although exhaustive research has been conducted on Asclepias flower morphology, seed production, and pollinator impact, little cytological work has been published. Knowing the genome size of species can predict their ability to hybridize and the potential of genetic variability within a genus. Our study used 15 different Asclepias species and four interspecific Asclepias hybrids, and the total genomic content was calculated using propidium iodide. We found the 2C genome size ranged from 0.65 to 1.24 picograms. To our knowledge, our research presents data on eight species with previously unknown genomic content and is the first to report 2C values for interspecific Asclepias hybrids.