The effect of the Z-isomer content on particle production of lycopene by the solution-enhanced dispersion by supercritical fluids (SEDS) process was evaluated. Using the thermal isomerization and filtering technique, lycopene containing a large amount of Z-isomers (65.3% and 97.8%) was prepared from (all-E)-lycopene. When (all-E)-lycopene was used as a raw material for SEDS precipitation, particles with an average size of 3.6 μm were obtained. On the other hand, when using lycopene containing a large amount of the Z-isomers, the lycopene particles became significantly finer compared with those obtained using (all-E)-lycopene. For example, when using lycopene containing 97.8% Z-isomers, uniformly sized particles with an average size of 75 nm were obtained. Interestingly, despite the Z-isomer content of the raw materials, the obtained lycopene particles were primarily in the thermodynamically stable all-E-isomer. Therefore, the Z-isomerization pre-treatment of lycopene is very effective to obtain uniform, stable, and fine particles using SEDS precipitation.