There is such a thing as an ODBC driver for Excel, which I think would allow you to execute SQL queries against a spreadsheet. However, I am not familiar with it.
I am more familiar with something called ClosedXML (which is open source despite the name). You can used it to open an .xlsx file and read the cells. It's also pretty handy for creating .xlsx files. Documentation and download at
http://closedxml.codeplex.com/[
^]. Rather than download it from there, you might want to get NuGet package.
ClosedXML only works with .xlsx files. If you have a .xls file, you can write code to load into Excel and save it as a .xlsx file. If you want the code for that just ask.