Once I have performed sheet = client.open_by_key('GoogleSheetKey').get_worksheet(0) does sheet.cell(1,1) perform another HTTP request to Google API? or is it working off a local object at that point? Thanks!
Yes, sheet.cell(1, 1) performs another HTTP request. This is by design: gspread is a "thin" API wrapper and leaves data caching to the end user.
However, if you modifying multiple cell values, consider batching the updates with Worksheet.update_cells method.