A molecular dynamics (MD) simulation-based study on the displacement-controlled fatigue behavior of Cu nanoparticles under ultra-high frequency fatigue cycling has been carried out. Effects of various fatigue parameters such as displacement amplitude, mean displacement, loading frequency, temperature, particle size, alloying, and surface condition on the fatigue life of Cu nanoparticles have been theoretically investigated. Results show that the fatigue life of Cu nanoparticles decreases with the increase in displacement amplitude and/or mean displacement, for a given loading frequency and temperature. Increase in the loading frequency reduces the fatigue life. Apart from this, it is observed that the fatigue life decreases slightly with the increase in temperature within the range from 298 to 370 K. Surface effect has been studied by providing a circumferential notch at the middle of the Cu nanoparticle. It is found that the presence of a surface notch reduces the fatigue life of the Cu nanoparticle to a great extent. It is also found that the fatigue life of Cu nanoparticle decreases with decrease in particle size. Furthermore, study on the effect of alloying on the fatigue life has revealed that alloying of the Cu nanoparticle with Ag causes enormous increase in the fatigue life. The present study may give an useful guideline to the design and development of nanoparticles for any given fatigue service condition under ultra-high frequency regime.