We investigated the quality of drinking water and its possible effects on human health in the Dera Ghazi Khan (D. G. Khan) district of Pakistan. Samples were collected from three tehsils of the D. G. Khan district, namely D. G. Khan, Kot Chutta, and Taunsa. A total of 50 samples (n = 50) were collected from the study area using standard procedures. The pH of the water samples ranged from 6.52–8.75, EC 0.31–9.78 dS m−1, and TDS 105–985 mg L−1. The bacterial analysis showed that 9 out of 50

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... s (18%) contained pathogenic E. coli bacterial. The results showed that the pH and EC values of some sampling sites exceeded the WHO guidelines for drinking water. It was observed that the pH of only 1 sample, and the EC of 18 samples in D. G. Khan—5 in Kot Chutta and 16 in Tehsil Taunsa—exceeded the WHO guidelines. In terms of E. coli presence and related diseases (hepatitis A, B, and C), we collected data, which were screened and belonged to the sampling sites, from 1378 patients receiving treatment related to hepatitis A, B, and C. It was revealed that 530 patients belonged to the D. G. Khan site, followed by Taunsa (460), and Kot Chutta (388). Based on the results, it was concluded that the quality of drinking water samples generally was good, except for 6% of the samples, assessed using (SAR) and Kelly's ratio (KR), and 9 sites were positive for E. coli.