The massive accumulation of organic matter, which periodically occurs in the northern Adriatic Sea, and in other locations worldwide, is presently thought to be the results of the aggregation of dissolved organic matter (DOM) into particulate organic matter (POM). This phenomenon is the result of human activities and propitious weather conditions. Although many aspects of the phenomenon are well understood, the trigger mechanisms leading to mucilage formation have not been clarified yet, probably as a consequence of inadequate analytical approaches. In this context, the recent advancements in LC-MS interfacing might contribute in clarifying the mechanism of mucilage formation. In the present paper, hydrophilic interaction liquid chromatography coupled with electrospray tandem mass spectrometry (HILC-ESI-MS/MS) is proposed as an innovative method for the investigation of underivatized oligosaccharides in mucilage samples. Recent findings suggest that the significant presence of these compounds in seawater can play an important role in the initial steps of the agglomeration processes forming gelatinous material. Our results reveal the presence of several maltodextrines in the water-soluble fraction of mucilage macroaggregates, collected in various locations of the northern Adriatic Sea. In our knowledge, the proposed method is the first application of LC-MS in the investigation of marine mucilage.