AbstractMany thermospheric mass density (TMD) variations have been recognized in observations and physical simulations; however, their impact on the low‐Earth‐orbit satellites has not been fully evaluated. The present study investigates the quantitative impact of periodic spatiotemporal TMD variations modulated by the empirical DTM2013 model. Also considered are two small‐scale variations, that is, the equatorial mass anomaly and the midnight density maximum, which are reproduced by the Thermosphere‐Ionosphere‐Electrodynamics General Circulation Model. This investigation is performed through a 1‐day orbit prediction (OP) simulation for a 400‐km circular orbit. The results show that the impact of TMD variations during solar maximum is 1 order of magnitude larger than that during solar minimum. The dominant impact has been found in the along‐track direction. Semiannual and semidiurnal variations in TMD exert the most significant impact on OP among the intra‐annual and intradiurnal variations, respectively. The zero mean periodic variations in TMD may not significantly affect the predicted orbit but increase the orbital uncertainty if their periods are shorter than the time span of OP. Additionally, the equatorial mass anomaly creates a mean orbit difference of 50 m (5 m) with a standard deviation of 30 m (3 m) in 1‐day OP during high (low) solar activity. The midnight density maximum exhibits a stronger impact in the order of 150±30 and 15±6 m during solar maximum and solar minimum, respectively. This study makes clear that careful selection of TMD variations is of great importance to balance the trade‐off between efficiency and accuracy in OP problems.