Propofol (2,6-diisopropylphenol) is probably the most widely used intravenous general anesthetic. In this work, the interaction of propofol dimer with 2-4 water molecules was analyzed. The molecular aggregates were formed using supersonic expansions, which maintain the molecules confined in a cold, collision-free environment. The clusters were then examined using a number of mass-resolved laser-based spectroscopic techniques, including 2-color REMPI (resonance enhanced multiphoton ionization), UV/UV hole burning and IR/UV double resonance. Two isomers were found for each stoichiometry, whose final structures were determined by comparison between the experimental data and those from density-functional-theory calculations (M06-2X/6-31+G(d)). The analysis of the observed structures allows to conclude that the water molecules always form hydrogen bond networks, whose contribution to the cluster's total binding energy increases with the number of water molecules. In the cluster with four water molecules, the two propofol molecules lose most of their contact points. In addition, the steric hindrance produces a change from cyclic to non-cyclic hydrogen bond networks earlier than in similar systems.