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Plant disease management is key to sustainable production of staple food crops. Calcium (Ca²⁺) signal and phytohormones play critical roles in regulating plant defense responses against pathogens. The Ca²⁺ signals are sensed, decoded and transduced by calmodulin and other Ca²⁺ -binding proteins, followed by interaction with and modulation of activities of target proteins such as calmodulin-binding proteins (CBPs). Members of the Arabidopsis <i>CBP60</i> gene family, <i>AtCBP60g</i> and <i>AtSARD1</i>, have emerged as major regulators of immune responses. In this study, we identified a 15 member <i>CBP60</i> gene family in rice (<i>Oryza sativa</i>) of which <i>OsCBP60g-3</i>, <i>OsCBP60g-4</i>, <i>OsCBP60a</i> and <i>OsSARD-like1</i> genes were consistently upregulated in rice seedlings in response to infection with both fungal (<i>Magnaporthe oryzae</i>) and bacterial (<i>Xanthomonas oryzae</i>) pathogens as well as by salicylic acid (SA). <i>OsCBP60g-4</i> and <i>OsCBP60g-3</i> were induced maximally by SA and brassinosteroid (BR), respectively, and <i>OsCBP60g-4</i> was expressed at 3-fold higher levels in the <i>M. oryzae</i> resistant rice genotype (IC-346004) as compared to the susceptible rice genotype (Rajendra Kasturi). The considerable expansion of the immunity clade and the up-regulation of several <i>OsCBP60</i> genes in response to pathogens and defense hormones supports the importance of further investigating <i>OsCBP60</i> genes as targets for increasing disease resistance in rice.