Abstract Composed of individual unit cells strategically arranged to achieve a desired function, lattices are a promising solution for laser powder bed fusion (LPBF) support structure design in additive manufacturing. Despite their many advantages (e.g., multifunctionality and reduced material cost), prior work in lattice support structure design primarily focuses on horizontal support domains that are not translatable to support domains for complex geometries, thereby limiting their application. This work introduces a multi-sized unit cell design optimization (MSO) method to create lattice support structures (LSS) for parts with complex geometries. The proposed method utilizes voxelization to generate LSS using box-like unit cells of different sizes. It also allows for efficient, high-dimensional design optimization for the types and locations of user-specified unit cells through a modified simulated annealing-based optimization algorithm. The effectiveness and efficiency of the MSO method are demonstrated through the case study of an adapter pipe for a high-temperature heat exchanger. For this demonstration, LSS using multi-sized unit cells are designed to increase heat transfer rate while satisfying structural integrity and material cost constraints. The case study results indicate that the design of the LSS derived from the MSO method fulfills all constraints, including the design constraint of 50% material cost reduction, compared to the solid support structure. In contrast, the lattice support structure designs derived from equal-sized unit cell methods either cannot satisfy all design constraints or have a lower heat transfer rate than the design of the MSO method.