Sigma (σ) receptor subtypes, σ<sub>1</sub> and σ<sub>2</sub>, are targets of wide pharmaceutical interest. The σ<sub>2</sub> receptor holds promise for the development of diagnostics and therapeutics against cancer and Alzheimer's disease. Nevertheless, little is known about the mechanisms activated by the σ<sub>2</sub> receptor. To contribute to the exploitation of its therapeutic potential, we developed novel specific fluorescent ligands. Indole derivatives bearing the <i>N-</i>butyl-3<i>H</i>-spiro[isobenzofuran-1,4'-piperidine] portion were functionalized with fluorescent tags. Nanomolar-affinity fluorescent σ ligands, spanning from green to red to near-infrared emission, were obtained. Compounds <b>19</b> (σ pan affinity) and <b>29</b> (σ<sub>2</sub> selective), which displayed the best compromise between pharmacodynamic and photophysical properties, were investigated in flow cytometry, confocal, and live cell microscopy, demonstrating their specificity for the σ<sub>2</sub> receptor. To the best of our knowledge, these are the first red-emitting fluorescent σ<sub>2</sub> ligands, validated as powerful tools for the study of σ<sub>2</sub> receptors via fluorescence-based techniques.