Abstract: China is accelerating the development of sodium-cooled fast reactor technology. For nuclear reactors, whether it is a pressurized water reactor or a fast reactor, core flow distribution is a key concern, which directly determines whether the reactor can operate safely and reliably. Sodium-cooled fast reactor core adopts a three-stage flow distribution method consisting of diagrid, distribution headers and assemblies. Distribution headers are installed on diagrid, and various types of assemblies are installed on distribution headers. Pressure drop of the core is composed of distribution header pressure drop and assembly pressure drop. The distribution header pressure drop itself affects the flow distribution of the assemblies, thereby affecting the safety of the core. Therefore, it is of great significance to study the impact of distribution header pressure drop on the flow distribution of assemblies for the sodium-cooled fast reactors. In order to reduce the flow distribution deviation of assemblies caused by the distribution header pressure drop, it is necessary to carry out a reasonable assembly pressure drop design. Based on the mechanism of flow distribution deviation of assemblies caused by distribution header pressure drop, a theoretical calculation model was proposed, and an optimized design of assembly pressure drop was carried out for the China Experimental Fast Reactor (CEFR) core. Based on the actual layout of CEFR core, the maximum deviation of flow distribution of fuel assemblies was obtained, and the optimization direction of nominal assembly pressure drop was determined, indicating that optimization design of nominal assembly pressure drop should be carried out for the first five rings. After adjusting the nominal pressure drop of the first five rings of assemblies from 250 kPa (the original nominal pressure drop) to 249 kPa, 248.5 kPa, and 248 kPa, respectively, the maximum deviation of flow distribution of fuel assemblies firstly decreases from −0.99% to −0.95%, and then increases to −1.02% and −1.08%, which indicates that nominal assembly pressure drop should be elaborately determined to obtain a minimum flow distribution deviation of fuel assemblies. In conclusion, when conducting core thermal hydraulic design for sodium-cooled fast reactors, it is necessary to analyze the optimization direction of nominal assembly pressure drop based on actual core layout, and sensitivity analysis should be conducted to finally determine the nominal assembly pressure drop to reduce the impact of distribution header pressure drop on flow distribution of assemblies to the lowest extent.