The aim of this paper is to propose a new framework for assessment of fatigue partial safety factors with focus on steel bridges welded joints. Fatigue resistance S-N curves for constant amplitude (CA) and variable amplitude (VA) loadings are defined using a novel probabilistic approach based on Maximum Likelihood (ML) and Monte-Carlo Simulations (MCS) methods. The proposed framework includes ML-MCS-based S-N curves of different welded detail categories and it is applicable for the case of deterministic and probabilistic CA loadings as well as for VA loadings. One example is developed, that of a typical bridge fatigue sensitive welded joint. The results are compared to Eurocode standards both in terms of partial safety factor values and of characteristic S-N curves.