hi ,
1. Check for missing indexes
2. Do you running rebuild index\reorg ,update statistics on weekend?
3.Try to find out which queries taking more cpu time from which application ?
4. Check for query optimization
5. Check the mdf files and ldf files in the same location
6. Run perfmon and check memory bottleneck and cpu bottleneck
7. Run a trace and find which queries are running during the site slowness
8 .Ask application team to check all app servers in load balancer or not ?
9.check for I\O operations [disk read and write per sec]
Thanks
Lavanya