Bacteria are constantly exposed to fluctuations in reactive oxygen species (ROS). In particular, pathogenic bacteria encounter elevated ROS-levels during host infection. In our present study we investigated the intricate regulatory interplay of the LysR-type transcriptional regulators LsrB and OxyR in Agrobacterium tumefaciens. OxyR is a widespread thiol-based redox sensor in bacteria, while LsrB is unique to Rhizobiales. Using phenotypic assays and RNA-sequencing under oxidative stress, we unveiled a central role for both regulators in co-regulating key antioxidant pathways, including katG encoding a bifunctional catalase/peroxidase. Furthermore, we provide novel insights into the mechanism of LsrB activation, suggesting that LsrB also functions as a thiol-based redox sensor. In summary, our findings illuminate the LsrB-OxyR system as a critical component of A. tumefaciens' defense against oxidative stress