High-precision cadmium (Cd) isotope compositions are reported for sphalerite, galena, and smithsonite from the Fule Zn-Pb-Cd deposit, a typical Mississippi Valley-type deposit in Southwest China. Dark sphalerite has lighter delta Cd-114/110 values (0.06 to 0.46 aEuro degrees) than light sphalerite (0.43 to 0.70 aEuro degrees), and the Cd in galena is primarily in the form of sphalerite micro-inclusions with delta Cd-114/110 of -0.35 to 0.39 aEuro degrees. From early to late stages, delta Cd-114/110 values of smithsonite regularly increase from 0.19 to 0.42 aEuro degrees, whereas Cd/Zn ratios decrease from 252 to 136; the delta Cd-114/110 variation pattern of supergene smithsonite reflects kinetic Rayleigh fractionation during low-temperature processes. From the bottom to the top of the orebody, the dark sphalerite has different patterns in delta Cd-114/110 values, Cd/Zn ratios, delta S-34 values, and Fe concentrations compared to the light sphalerite, indicating that dark and light sphalerite formed by different processes. The varying patterns of delta Cd-144/110 values and Cd/Zn ratios within light sphalerite are similar to those of layered smithsonite, and the delta Cd-144/110 values have a positive correlation with delta S-34 values, indicating that Cd isotope fractionation in the light sphalerite was due to kinetic Rayleigh fractionation. Instead, in dark sphalerite, the delta Cd-144/110 values have a negative correlation with delta S-34 values and a positive correlation with the Cd/Zn ratio. Thus, it can be concluded that dark sphalerite could be modeled in terms of two-component mixing (basement fluid and host-rock fluid), which is in agreement with previous explanations for the negative correlation between delta Zn-66 and delta S-34 in some typical Zn-Pb deposits. We propose that the significant variation in Cd isotope composition observed in the Fule Zn-Pb-Cd deposit confirms that Cd isotopes can be used for tracing fluid evolution and ore formation.