AtNHR2A and AtNHR2B were identified in Arabidopsis thaliana as two immune proteins given the susceptibility of the single mutants Atnhr2a and Atnhr2b to Pseudomonas syringae pv. tabaci (Pstab), a pathogen that does not infect wild-type Arabidopsis plants. Notably, the double mutant Atnhr2b Atnhr2a exhibited even greater susceptibility to Pstab than either single mutant, indicating that AtNHR2A and AtNHR2B function together in plant immunity. The subcellular localization of AtNHR2A and AtNHR2B to endomembrane compartments and their interaction with proteins known to be secreted led us to hypothesize that these two proteins participate in immune-related secretory processes. To investigate this, we isolated apoplastic fluid from the double mutant Atnhr2b Atnhr2a and the wild-type Col-0 for comparative proteome analysis. Using quantitative proteomics, we identified 52 Differentially Abundant Proteins (DAP) with N-terminal signal peptides in the apoplast of Atnhr2b Atnhr2a compared to Col-0, with ~50% showing lower abundance in Atnhr2b Atnhr2a, highlighting that Atnhr2b Atnhr2a is compromised in conventional protein secretion. Additionally, we developed an analytical pipeline to identify secreted proteins lacking signal peptides significantly enriched in the apoplast, revealing 59 previously unknown proteins whose secretion is dependent on AtNHR2A and AtNHR2B through a non-conventional secretory pathway. The differences in protein abundance within the apoplastic compartment provided compelling evidence that AtNHR2A and AtNHR2B are key mediators of the secretory pathway involved in plant immune response.