Vaccines as most effective intervention are considered integral part in preventing the pandemics and infective diseases. The major hurdle in the appropriate management of COVID-19 was considered as hesitancy to vaccination. The population had no previous knowledge and experience of such vaccines therefore current study was conducted. A descriptive and cross-sectional study for a period of four months from Jan-Apr 2021 was conducted. One thousand samples had recruited on the basis Rao-soft formula. The confidence interval was 95% with + 5% limitation error. A series of questions were prepared related to knowledge and acceptance of COVID-19 after an extensive literature survey. The data has descriptively analyzed by using standard parameters. The demographic detail of 1000 participants showed that majority were males 61.2% (n=612), while 38.8% (n=388) were females. The more percipients were found with age group of 31-50 years 43.6% (n=436). The most common reason was concluded as lack of awaraness/lack of knowledge 39.5%, however the other contributing factors were fear of adverse effects/side effects 14.1%, and not taking the Pandemic as myth 30.1%. The least common reason was unneccesary use of vaccine as population belived that administration of vaccine does not make any difference. The current study indicated that the Participants of the study had moderate level of education in different cities of Sindh Pakistan, However the population’s intension towards the acceptance of vaccines are somehow unfavorable. The health provider must activate their role to educate and clear the safety profile of vaccines. This could be achieved by several campaigns, educational programs and counselling sessions.