Updated project metadata. The protein kinase OXI1 is induced by a large number of stress conditions and regulates the interaction of plants with pathogenic and beneficial microbes but little is yet known on the underlying mechanisms. In this work, we generated Arabidopsis OXI1 knock out and overexpression lines and show by transcriptome, proteome and metabolome analysis. Our work revealed that OXI1 regulates biosynthesis of SA via CBP60g-induced expression of isochorismate synthase SID2. OXI1 also induces the transcription factor WRKY33 and its downstream target PAD3, resulting in accumulation of camalexin. Moreover, OXI1 regulates ALD1, SARD4 and FMO1 to promote the biosynthesis of pipecolic acid (Pip) and N-hydroxy pipecolic acid (NHP), mediating systemic acquired resistance to bacterial infection. In contrast to OXI1 overexpressor plants, OXI1 knock out plants show enhanced expression of nuclear and chloroplast genes of photosynthesis, and accordingly enhanced growth under ambient conditions. Overall, these results show that OXI1 plays a key role in regulating the trade-off between growth and defense in plants.