The size of a packet has a strong influence on the quality of wireless data communications. In traditional wireless networks, there is an inherent trade-off in determining the packet size. First of all, compared with long packets, short packets are less likely to be affected by the error-prone wireless channels. However, short packets suffer overhead due to headers. In mobile cognitive radio (CR) networks, determining the secondary user (SU) packet size becomes much more complicated and critical. In addition to all the impacts in traditional wireless networks, the primary user (PU) activity and the mobility of SUs and PUs have significant impacts on the SU packet size. Moreover, the channel fading caused by the SU mobility also has an impact on the SU packet size. More importantly, all these impacts on SU packet size constantly vary with time and space, which makes this issue extremely challenging. Without a careful design of the SU packet size, both SU and PU transmissions may suffer severe performance degradation. In this paper, the optimal SU packet size issue in mobile CR networks under fading channels is studied. We mathematically model these impacts and derive the optimal SU packet size. To the best of our knowledge, this is the first work that systematically investigates the optimal SU packet size issue in mobile CR networks.