When phospholipids are dispersed in water and sonicated for approx. 240 min, vesicles (liposomes) of 40–45 nm in diameter are formed. Their steric stabilization is achieved by the addition of (tri)-block copolymers of the A-B-A type (A is PEO and B is PPO). Importance is placed on the way the copolymer was added to the vesicles. Stabilization is thought to be optimized when adding the copolymer initially, therefore allowing participation between the latter and phospholipid molecules towards vesicle formation, leading to the physical anchoring of the hydrophobic homopolymer (PPO) into the bilayer. In contrast, when the copolymer molecules were added after vesiculation was complete, stabilization was not optimum. The effect of a monovalent (NaCl) and a divalent (MnCl2) cation on the vesicle systems was systematically studied by dynamic light scattering (PCS) and turbidity measurements. The effect of electrolytes was studied by: a) increasing the cation concentration only in the outer vesicle aqueous phase, monitoring the occurring flocculation of the vesicles, and b) forming the vesicles in high electrolyte concentration and diluting, therefore creating an osmotic gradient between the two aqueous phases. Vesicle flocculation caused by NaCl or MnCl2 occurred in all systems, but the ones coated with copolymers required higher electrolyte concentrations. When an osmotic gradient developed between the vesicle inner and outer aqueous phases, resistance against swelling was observed only in the case of vesicle systems formed in the presence of copolymers. In both electrolytes (NaCl and MnCl2) coating the vesicle surface with polymer molecules resulted in increased protection against flocculation. Moreover, the initial addition of block copolymers produced vesicles that could sustain osmotic swelling.