Fluid infusion systems and fluid couplings are described herein. The infusion systems may include one or more fluid couplings used to make fluidic connection between a supply line and delivery tubing. The fluid couplings separate the functions of providing a seal around a delivery tube and retaining the delivery tube within the fluid coupling. The seal provided around the delivery tube prevents leakage around an exterior surface of a delivery tube such that fluid passing through the coupling must pass through the delivery tube rather than leak around the delivery tube. The structure used to retain the delivery tube in the fluid coupling prevents ejection of the delivery tube from the coupling due to the fluid pressures present in the coupling. The separate functions are performed by different structures within the fluid couplings.