Abstract Within the framework of magnetic confinement fusion, several projects worldwide are demonstrating the possibility of integrating high-temperature superconductors (HTS) in the coil systems. HTS-based technologies are highly attractive for practical applications because they can extend the operating margins of fusion coils in terms of higher temperatures, transport currents and magnetic fields. Based on the results achieved with the twisted-stacked tape cable, we have designed a novel low-loss HTS sector cable-in-conduit conductor, with a target of 60 kA at 4.5 k, 18 T, which is presently of interest for the DEMO Central Solenoid coil. In HTS cables, the AC losses can represent a significant limiting factor, therefore they must be taken into consideration both in the design phase and in the assessment of the overall magnet thermal budget. In this work, to assess the loss behavior and to optimize the cable design, we have explored different aspect ratios and arrangements of the stacked tapes within the cable layout. The magnetization losses are calculated with a 2D finite-element model based on the T-A formulation and analytical approximations based on the Brandt-Halse critical state model. Specifically, we have developed an analytical formulation that allows for the calculation of the instantaneous power losses in HTS stacked cables with a limited number of tapes per stack, achieving sufficient accuracy at high fields. The analytical model enables a sufficiently accurate assessment of the heat deposited on the conductor during those particular instants of a plasma scenario where the variation of the field is very high, such as during the critical initial discharge period of the plasma initiation.