Last month, I was working on an Excel file that contains about 0.7 million VLOOKUP() formulas over 4000 and 48000 rows ranges. Opening on my machine takes over 2 hours with 100% CPU usage and any editing was painfully slow. Such operation can easily suck up the power of your server. (In the end I rewrite the file to use VBA instead and the calculation completed within 5 seconds.)
Make sure that calculation options is set to manual, if you are making changes to data related to vlookups. I can't underestimate the importance of this.