During the last decade, graphene has emerged as one of the most researched material with promising applications in photocatalysis, molecular sensing, nanoelectronics, and energy storage. Here we show the incorporation of substitutional dopants significantly affects the graphene chemical reactivity. B and N dopants locally reduce and increase respectively the interaction of graphene to individual CO molecules attached to the apex of metallic tip, used for performing scanning probe microscopy and atomic force microscopy. The interaction is driven by weak electrostatic forces between seated charges induced by dopants in graphene and the molecule. The doping is accompanied by a sharp redistribution of graphene electron density at the B-C and N-C bonds observed in high-resolution AFM images and subsequent variation of the work function. Our observations provide further insight into the non-covalent interactions of boron and nitrogen dopants in graphene with relevant molecules for potential applications in molecular sensing.During the last decade, graphene has emerged as one of the most researched material with promising applications in photocatalysis, molecular sensing, nanoelectronics, and energy storage. Here we show the incorporation of substitutional dopants significantly affects the graphene chemical reactivity. B and N dopants locally reduce and increase respectively the interaction of graphene to individual CO molecules attached to the apex of metallic tip, used for performing scanning probe microscopy and atomic force microscopy. The interaction is driven by weak electrostatic forces between seated charges induced by dopants in graphene and the molecule. The doping is accompanied by a sharp redistribution of graphene electron density at the B-C and N-C bonds observed in high-resolution AFM images and subsequent variation of the work function. Our observations provide further insight into the non-covalent interactions of boron and nitrogen dopants in graphene with relevant molecules for potential applications in molecular sensing.