A time-of-use activated syringe assembly includes a syringe barrel defining a chamber, a plunger rod having a forward attachment end located within the chamber of the barrel, and a stopper located within the chamber of the barrel and including a rearward end adapted to receive the plunger rod. The stopper includes a first perimetrical skirt extending around an outer circumference thereof and extending toward a front end of the stopper. An activation mechanism is associated with at least one of the stopper and the plunger rod, and the plunger rod is configured for transition between a pre-loaded position in which the activation mechanism is unactivated and a loaded position in which the activation mechanism is activated. Upon activation, the activation mechanism applies a radial force to the first perimetrical skirt causing the skirt to seal against an inner wall of the syringe barrel.