You'll need the Python Win32 extensions - http://sourceforge.net/projects/pywin32/
(now migrated to GitHub: https://github.com/mhammond/pywin32)
Then you can use COM.
from win32com.client import Dispatch
excel = Dispatch('Excel.Application')
wb = excel.Workbooks.Open(r'c:\path\to\file.xlsx')
ws = wb.Sheets('My Sheet')
# do other stuff, just like VBA
wb.Close()
excel.Quit()
You can put your script on Windows Task Scheduler to run for the times you need.