Lipid droplets (LDs) are intracellular organelles that play a vital role in the replication of some viruses, and have more recently been implicated in the TLR7/9 innate signalling response to viral infection. Despite their wide range of signalling roles in various metabolic pathways, LDs have been overlooked as potential organelle platforms for innate signalling events. Here we have shown for the first time, that LDs play a role in the outcome of the early innate host response to viral infection, independent of TLR7 and 9. This study established an in vitro model to evaluate the efficiency of the early innate immune response in cells with reduced LD content to dsDNA/dsRNA viral mimics and Sendai viral infection, utilising RT-qPCR for IFN-β, IFN-λ and specific interferon stimulated genes (ISGs) in conjunction with luciferase based reporter assays. Cellular LD content did not alter the entry of fluorescently labelled viral mimics into cells, but significantly decreased the ability of both Huh-7 and HeLa cells to produce type I and III IFN, as well as downstream ISG expression, indicative of an impeded innate immune response. This observation was also seen during Sendai virus infection of HeLa cells, where both control and LD reduced cells replicated the virus to the same level, however, cells with reduced LDs presented a significantly impaired type I and III IFN response. In addition to altered IFN production, cells with reduced LD content exhibited decreased expression of specific antiviral ISGs: Viperin, IFIT-1 and OAS-1 under IFN-β stimulation; however the overall induction of the ISRE-promoter was not affected. This study implicates a role for LDs in the production of an efficient early innate host response to viral infection and future work will endeavour to determine the precise role these important organelles play in induction of an antiviral response.