Solid phase microextraction (SPME) coupled to gas chromatography-mass spectrometry (GC-MS) was employed for the headspace determination of the volatile organic fraction emitted by two of the most common Mediterranean demosponges, Ircinia variabilis and Sarcotragus spinosulus, and of indole and some biogenic amines released by sponges in an aqueous medium. A total of 50/30 µm divinylbenzene/carboxen/polydimethylsiloxane and 75 µm carboxen/polydimethylsiloxane fibers were used for the headspace extraction of low molecular weight sulfur compounds from a hermetically sealed vial containing sponge fragments, while the direct immersion determination of indole and biogenic amines was performed. The biogenic amines were extracted after in-solution derivatization with isobutyl chloroformate. All analytical parameters (linearity, limits of detection, and quantification, precision, and recovery) were evaluated for indole and biogenic amines. SPME-GC-MS proved to be a reliable means of highlighting the differences between molecules released by different sponges, principally responsible for their smell. The combined approaches allowed the identification of several volatile compounds in the headspace and other molecules released by the sponges in an aqueous medium, including indole and the BAs cadaverine, histamine, isobutylamine, isopentylamine, propylamine, 2-phenylethylamine, putrescine and tryptamine. The results obtained represent a further contribution to the picture of odoriferous molecules secreted by sponges.