Topology optimization (TO) was conducted for three dimensional static fluid mixers. The problem is optimized using the weakly coupled Navier-Stokes equation at low Reynolds number (Re ≤ 1) and a convection-diffusion equation. The domain was discretized with up to 10 million cells. The optimizations were run with 1024 to 2048 CPUs on a national supercomputer. For a mixer in a square cross-section channel, the mixing was improved by 83% for a modest 2.5 times higher pressure drop compared with the open straight channel. For a cylindrical cross-section tee arrangement, the mixing improved by 91% with a 2.5 times higher pressure drop compared to the straight channel.