If you are using SQL accounts then slowdowns are unlikely to be caused by different domains.
You should follow standard performance troubleshooting procedure. Run a trace using the profiler. Use the tuning template and add the Application Name, Hostname, CPU, Reads, and Writes columns. Filter on the duration column, e.g. greater or equal than 10.000 ms. Also group by by the Hostname and Application Name columns. Start the trace and then try to reproduce the problems.
If you see high CPU, Reads, and or Writes value there is probably a SQL Server issue related to the number of queries, complexity of queries, missing indexes, incorrect usage of indexes, execution plan (re)compiles, or IO congesting that needs to be solved. Otherwise it might be a locking (waiting for resources locked by other sessions), networking, or otherwise external issue.