Invertebrate iridescent virus 6 (IIV-6) is a nucleocytoplasmic virus with a 212 kb-long linear double-stranded DNA genome that encodes 215 putative open reading frames. The IIV-6 virion-associated proteins consist of at least 54 virally-encoded proteins. One of our previous findings showed that most of these proteins are encoded by genes from the early transcriptional class. This indicates that these structural proteins may not only function in the formation of the virion, but also in the initial stage of viral infection. In the current study, we followed the protein expression profile of IIV-6 over time in Drosophila S2 cells by label-free quantitation using a proteomic approach. A total of 95 viral encoded proteins were detected in infected cells, of which 37 are virion proteins. The expressed IIV-6 virion proteins could be categorized into three main clusters based on their expression profiles. These clusters were: 1) proteins with stably low or 2) exponentially increasing expression levels during infection, and 3) proteins that were initially highly abundant, but showed slightly reduced levels after 48 hours (h) post infection (p.i.). Here, we provide novel information on the kinetics of virion and infected cell-specific protein levels that assists in understanding gene regulation in this lesser known DNA virus model.