Depletion calculations and related sensitivity analyses are fundamental in designing nuclear reactors. Looking at the core design of liquid metal–cooled fast reactors, a novel procedure based on the Generalized Perturbation Theory was developed and implemented in the deterministic ERANOS suite to extend its current capabilities related to depletion-related sensitivity analysis. Specifically, a partial perturbative coupling of the burnup equations was introduced to estimate the sensitivities of final isotopic concentrations to microscopic cross sections. First, the procedure was successfully verified through a simple test case by comparing its results with an analytical solution obtained via MATLAB©. Then, a more complex case was studied to highlight the differences between the new perturbatively coupled configuration and the default decoupled one. Overall, the coupling proved to have a nonnegligible impact on the sensitivity coefficients, opening the path for further extending the procedure and applying it to more realistic problems.