A fluid infusion system that is configured to infuse fluid from a source to a patient. The fluid flows through tubing formed of one or more tube segments that define a fluid lumen. At least a portion of the tubing has a multi-layered configuration including an outer layer and an inner layer. The outer layer has one or more characteristics that are particularly suited for an outer layer such as to resist the environmental conditions that the tubing may experience. The inner layer is formed of a material that is compliant and resilient such that the inner layer may adapt to variations in fluid pressure during pumping of fluid through the tubing