A duodenal sleeve assembly comprises a sleeve, an expandable sealing member, a tether, and an expandable anchor. The sleeve is secured to the sealing member. The tether couples the anchor with the sealing member. A deployment instrument comprises a shaft assembly, a first retention member, and a second retention member. The first retention member selectively secures the sealing member to the shaft assembly. The second retention member selectively secures the anchor to the shaft assembly. When the first retention member is released, the sealing member expands outwardly to seal the proximal end of the sleeve against the mucosa of the patient's duodenum. When the second retention member is released, the anchor expands outwardly within the stomach to anchor the sleeve assembly relative to the stomach. The tether traverses the pylorus. The sleeve isolates chyme from enzymes in the duodenum; and the mucosa of the duodenum from nutrients in the chyme.