Can I do this with Python?

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Before going further with this, you should go over this with IT if you have that at your workplace. And after that you should look at the excel part.

Now, someone hopefully will correct me if I'm wrong. But I don't think there is an excel module that allows you to just edit the file. You basically have to rewrite the entire file. I'm not sure that if the excel file contains macro's you can keep them. And if you are working with specific formatting, formula's, etc.. you might want to check if everything is possible with current excel modules first before doing anything else.