This work investigates the relationship between the multiphase microstructure and the macroscale fatigue behaviour of a cast super duplex stainless steel (SDSS). The microstructure of a cast SDSS is typically composed of a FCC γ-phase and a BCC δ-phase. However, deleterious secondary phases (SP), such as sigma and chi, may precipitate when SDSS is exposed to high-temperature ranges, jeopardising its mechanical properties, namely fatigue performance. The purpose of this investigation was to quantify the correlation between SP amounts and fatigue life of a cast SDSS (CD3MWCuN, ASTM A890). Fatigue tests were conducted using miniature specimens taken from a cast C-Ring with different SP amounts. A numerical model was proposed to calibrate the fatigue test parameters. After the tests, SEM and EBSD techniques were used to quantify the SP and analyse the fatigue-crack propagation. The microstructural analysis was complemented with hardness and tensile tests. Regression models were developed to correlate the percentage of SP, the fatigue resistance and the number of cycles to failure, and to predict the microstructural stress concentration from the amount of SP. In addition, a methodology is proposed for predicting S-N curves as a function of the amount of SP, showing a high correspondence in the increase of the percentage of SP with the decrease in fatigue life. Furthermore, the fatigue strength, for a given number of cycles to failure, tends to decrease linearly with increasing the SP, while the microstructural stress concentration factor tends to increase with an increase in SP. These findings contribute to further knowledge on predicting the behaviour of cast SDSS under different cyclic conditions, which can be valuable for optimizing design and performance in various applications.