Limited evidence associates inadequate classroom ventilation rates (VRs) with increased illness absence (IA). We investigated relationships between VRs and IA in California elementary schools over two school years in 162 3rd–5th-grade classrooms in 28 schools in three school districts: South Coast (SC), Bay Area (BA), and Central Valley (CV). We estimated relationships between daily IA and VR (estimated from two year daily real-time carbon dioxide in each classroom) in zero-inflated negative binomial models. We also compared IA benefits and energy costs of increased VRs. All school districts had median VRs below the 7.1 l/s-person California standard. For each additional 1 l/s-person of VR, IA was reduced significantly (p<0.05) in models for combined districts (−1.6%) and for SC (−1.2%), and nonsignificantly for districts providing less data: BA (−1.5%) and CV (−1.0%). Assuming associations were causal and generalizable, increasing classroom VRs from the California average (4 l/s-person) to the State standard would decrease IA by 3.4%, increase attendance-linked funding to schools by $33 million annually, and increase costs by only $4 million. Further increasing VRs would provide additional benefits. These findings, while requiring confirmation, suggest that increasing classroom VRs above the State standard would substantially decrease illness absence and produce economic benefits.