Just a quick blog post seems relevent after some problems were encountered with our SEPM server. After finding preformance lacking a bit on our SEPM server, I fired up the disk defragmenter. Despite having run it not that long ago, the drive was heavily fragmented. Our server has 60 GB of space, was about 2/5ths full, and was well over 40% fragmented. I setup a task to defrag the drive daily during the early morning hours. Since then, we haven't had a problem with fragmentation on the SEPM server.
Just some background. Our SEPM server is running Server 2003 x86 and SEPM RU5. I suspect due to the database backups and the regular definition downloads, that SEPM, by its nature, has a tendency to fragment drives rapidly.