VelA (or VeA) is a key global regulator in fungal secondary metabolism and development which we previously showed is required during the symbiotic interaction of Epichloë festucae with perennial ryegrass. In this study, comparative transcriptomics analyses of ΔvelA mutant compared to wild type E. festucae, under three different conditions (in culture, infected seedlings and infected mature plants) were performed to investigate the impact VelA on the E. festucae transcriptome. These comparative transcriptomics studies showed that VelA regulates the expression of genes encoding proteins involved in membrane transport, fungal cell wall biosynthesis, host cell wall degradation and secondary metabolism, along with a number of small secreted proteins and a large number of proteins with no predictable functions. In addition, these results were compared with previous transcriptomics experiments studying the impact of LaeA, another key global regulator of secondary metabolism and development that we have shown is important for the E. festucae- perennial ryegrass interaction. The results showed that although VelA and LaeA regulate a sub-set of E. festucae genes in a similar manner, they also regulated many other genes independently of each other suggesting specialised roles.