Infectious Bronchitis Virus (IBV) infection poses significant challenges to poultry health and production. This study investigates the modulation of inflammatory cell death pathways in IBV-infected macrophages through inhibiting either caspases or COX-2/PGE2 pathway. We measured intracellular and extracellular viral genome loads, cell viability, apoptosis, and necroptosis after infecting cells with two disparate IBV strains, respiratory Conn A5968 and nephropathogenic DMV/1639. Our findings demonstrated that reducing serum concentrations in culture media led to a substantial increase in viral genome load, accompanied by decreased cell viability, and heightened apoptosis and necroptosis in IBV DMV/1639 and IBV Conn A5968 infected cells, with the most pronounced effects observed in serum-free conditions. Apoptosis inhibition minimally affected intracellular viral genome loads for both IBV strains but significantly altered extracellular viral genome loads, depending on the specific caspase inhibitors employed. Inhibition of the COX-2/PGE2 pathway resulted in a notable reduction in intracellular viral genome loads for both IBV strains, with varied effects on extracellular viral genome load, particularly evident in the DMV/1639 strain. Furthermore, caspase-1/4 inhibitors exacerbated apoptotic pathways and broad caspase inhibition by using z-VAD-FMK mitigated virus-induced necroptosis. These findings shed light on the complex interplay between IBV infection and host immune responses, offering insights into potential therapeutic targets to mitigate IBV pathogenesis.