In the present study, magnetic core shell manganese ferrite nanoparticles-screen printed electrode (MCSNP/SPE) was fabricated and applied for the determination of the epinephrine (EP) in the presence of acetylcholine (ACh). The electrochemical behavior of epinephrine (EP) was studied by cyclic voltammetry, square wave voltammetry and chronoamperometry. The MCSNP/SPE had electrocatalytic activity toward the EP oxidation higher than bare SPE. It has been found that under an optimum condition, the oxidation of EP at the surface of MCSNP/SPE occurs at a potential about 70 mV less positive than that of an unmodified SPE. Based on the results, the linear oxidation peak current was 0.3–300 μmol L−1 and the correlation coefficient was obtained to be 0.999. According to the three times standard deviation (3Sb) of the blank, the detection limit was calculated 0.08 μmol L−1. Our results showed an increase in selectivity, stability and reproducibility for the MCSNP/SPE, which significantly could measure EP and ACh in EP ampoule, urine and serum samples. It can be concluded that the MCSNP/SPE has promising capacity in developing the electrochemical sensors.