In this study, a thermo-economic analysis was carried out for using Air-Side Economizer (ASE), Water-Side Economizer (WSE) and Combined Air or Water Economizer (CAWE) operation mode in order to cool a data center in ten cities of Iran with various weather conditions. The energy and cost saving potentials in Mashhad municipality's data center was studied as a case study and the findings were generalized for all cities during a year. The results showed that there are energy and cost savings potential by employing CAWE operation mode for all cities except coastal cities. In addition, the Power Usage Effectiveness (PUE) of the data center can be improved by a range from 10% to 12% using CAWE cooling mode for most cities. Finally, it was found that economic index of relative net present value (RNPV) for ASE, WSE and CAWE will be positive if their relative annual potential (RAP) are higher than 12%, 23% and 35%, respectively.