Quantum dots (QDs) are particularly valuable nanostructures for photodynamic therapy (PDT) applications due to their capacity of generating cytotoxic species, e.g. singlet oxygen (SO), when they are activated by light. We synthesized water-stable QDs with different composition (not doped and doped Cd- and Zn-based QDs) and surface chemistry (using different thiols compounds) under microwave irradiation heating conditions. As-synthesized QDs were optically characterized using UV–vis and photoluminescence spectroscopy techniques. The generation of SO species as a function of illumination time in the presence of the QDs dots was indirectly determined using a singlet oxygen sensor green (SOSG) kit. The corresponding constant rate “k”, associated to the generation of SO, was estimated for the different kind of materials and synthesis conditions. Results evidenced that the generation of SO was strongly dependent on the intrinsic composition, surface chemistry, type of doping species, and concentration of the QDs. The k values determined at 45 μg/mL of Thioglycolic acid (TGA)-capped Cd-based QDs and TGA-capped Zn-based QDs were, respectively, 1.15 × 10−2 ± 3.14 × 10−4 and 3.28 × 10−3 ± 8.75 × 10−5. Obtained results evidenced the capability of thiol-functionalized QDs to produce SO directly in aqueous phase, which increases their attractiveness as direct photo-sensitizers for 2-photon PDT applications.