In the Oinofita region, there was strong evidence of air pollution and hexavalent chromium (Cr(VI))-contaminated drinking water due to the increased number of industries, in contrast to the closely-located region of Arachova, which served as a control. To examine the health effects of environmental pollution, we performed an ecological study to compare the all-cause and cause-specific mortality. We considered the registered citizens of both study areas during an 11-year period (1999-2009) and we used the direct method of standardization to calculate the age, gender and period standardized rates (ASRs) and the standardized rate ratios (SRRs), using the greater Prefecture of Voiotia as the standard population. Statistically significantly higher rates of all-cause mortality (SRR = 1.22, 95% confidence intervals (CI) 1.1-1.4), cardiovascular (SRR = 1.36, 95% CI 1.1-1.7) and cerebrovascular diseases (SRR = 2.93, 95% CI 1.8-4.8) were identified for Oinofita compared to Arachova. Furthermore, suggestive results were found for cardiopulmonary diseases among males (SRR = 1.52, 95% CI 1.0-2.4) and leukaemias (SRR = 4.65, 95% CI 0.9-25.3). Elevated SRRs, not statistically significant though, were also observed for respiratory diseases, all cancers and specific cancer sites (lip, oral cavity and pharynx, liver, stomach, pancreas, lung, prostate, colon and kidney and other genitourinary organs among females). Increased mortality rates in the Oinofita region support the hypothesis of adverse health effects association with air pollution and Cr(VI)-contaminated drinking water. Further studies are needed to determine if this association is causal and to establish preventive guidelines and public health recommendations.