Howdy. That depends. Often when saving XL creates additional temp files that still attach to the .xls file. I use FastExcel from DecisionModels and use the "Clean Workbook" routine. That gets rid of all temp files, unused styles, number formats, etc.
Alternatively, do you have many formulas in the workbook? Are they efficient formulas, or resource hogs?
old, slow, and confused
but at least I'm inconsistent!