This study investigates the metal-silicate partitioning of Pb and U (DPb and DU, respectively) during core-mantle differentiation of terrestrial planets. For this, we equilibrated a molten CI-chondrite model mantle-composition with various Fe-rich alloys in the system Fe-C-Ni-Si-S in a multi-anvil over a range of P, T, fO2 (3-8 GPa, 2073-2373 K and from 1.5 to 5 log units below the iron-wüstite (IW) buffer). The chemical compositions of the run products and contents in Pb and U trace elements were determined using electron microbe and laser ablation inductively coupled plasma-mass spectrometry, respectively. We combined our new data set with pre-existing results in similar chemical systems to refine the major parameters controlling the DPb and DU values, based on thermodynamical calculations. We show: (i) a significant increase of the metal-silicate partition coefficients, from ∼1 to ∼50 for DPb and from ∼10−5 to 10−2 for DU with the addition of sulfur. (ii) At a fixed fO2, the presence of C in the metal favors U and Pb partitioning toward the silicate melt, when S produces the opposite trend. (iii) Temperature plays a non-negligible role in DPb value. Although the results suggest that the Pb depletion observed in the present-day bulk silicate Earth can be explained by core-mantle segregation at high-pressure in a deep-magma ocean, at conditions similar to that previously refined based on the behavior of many siderophile elements, such as Ni and Co, we will also discuss the possibility of late S-rich phases segregating to the core.