Selected ion flow tube – mass spectrometry (SIFT-MS) is based on chemical reactivity of analytes with reactant ions. The complete understanding of all the ion–molecule reactions is the key to the deployment of this technology for the direct and rapid analysis of VOCs in the gas phase. In the present work, we focused on direct analysis of carboxylic acids and esters, compounds involved in many biochemical processes. The ion–molecule reactions of negative precursor ions (OH–, O●−, O2●−, NO2– and NO3–) with 9 carboxylic acids and 21 esters were investigated in order to provide product ions and rate constants for these compounds analysis by SIFT-MS. The modelling of ion–molecule reaction paths by ab-initio calculations supported the experimental results and provided a better understanding of these gas phase ion–molecule reactions. The most common reaction mechanism with all the tested molecules is deprotonation. However, other specific reactivities, leading to the formation of anion-molecule complexes with NO2– and O2●− in particular, are observed. Furthermore, specific fragmentations of chemical families are also noticed and confirmed with O2●− and O●−. Finally, we demonstrated that the composition of the matrix (H2O, CO2) participates in the formation of secondary ions. In this work, we determined the kinetic rate constants in the nitrogen carrier gas and the detection limits of all the compounds with the eight precursor ions used by SIFT-MS, allowing accurate quantification in the gas phase at the ppb level. These results contribute to enlarge the negative ionization SIFT-MS measurements to applications where quantification of organic acids and esters are required.