The microstructure of an Al-Cu-Li alloy sheet is characterised in the solution treated, underaged, and peak aged tempers. Its mechanical response under uniaxial tension is measured at (Formula presented.), (Formula presented.), and (Formula presented.) along (Formula presented.), (Formula presented.), and (Formula presented.) to the rolling direction. The anisotropic stress-strain curves are interpreted using a polycrystal plasticity model, which implements three hardening modes suggested by the microstructure, viz., matrix hardening, hardening due to isotropic precipitates, and hardening due to anisotropic precipitates. Phenomenological activation theory based analysis of the work hardening suggests that the physical mechanism underlying work hardening due to anisotropic precipitates remains constant over the temperature range studied, while the mechanism underlying matrix hardening varies strongly with temperature. © 2020 Informa UK Limited, trading as Taylor & Francis Group.