Hi Jonathan,
Could you please provide the following information to us?
1. SEPM version? Number of SEPM's ? Is there any replication or failover/load balancing?
2. Number of SEP clients in the network managed by SEPM?
3. Size of database i.e.sem5.db?
4. Total diskspace allocated to C drive?
5. If it's SEP 12.1 version then have you enabled database maintenance options?
Above questions answer can help to narrow down the correct answer.
Please go through following articles also.
Changing the log settings to reduce the size of the database
http://www.symantec.com/docs/TECH105238
Article for references:
Best Practices for configuring the number of content revisions to keep in Symantec Endpoint Protection Manager:
http://www.symantec.com/business/support/index?page=content&id=TECH92225
SEPM server running out of disk space
https://www-secure.symantec.com/connect/forums/sepm-server-running-out-free-disk-space
Symantec Endpoint Protection Manager 12.1 database using a high amount of Hard drive space
https://www-secure.symantec.com/connect/articles/symantec-endpoint-protection-manager-121-database-using-high-amount-hard-drive-space