Background and Objectives. This study was conducted to assess the level of intention of the general public towards blood donation and the factors associated with it. Methods. A descriptive cross-sectional study was conducted in South-East Botswana amongst participants aged 21–65 years. An interviewer-administered questionnaire was completed for 384 participants. Results. Of the 384 participants, 104 (27.1%) reported that they had donated blood in the past and 269 (70.1%) stated that they were willing to donate blood in the future. Thirteen out of the 104 past donors (12.5%) reported that they had donated blood in the 12 months preceding the survey and only 10 (9.6%) participants reported that they have been regular donors. In the backward logistic regression analysis, the variables that remained significant predictors of the intention to donate blood were secondary education (adjusted odds ratio (AOR) (95% confidence interval (CI)): 2.92 (1.48, 5.77)), tertiary education (AOR (95% CI): 3.83 (1.52, 9.62)), and knowing a family member who had ever donated blood (AOR (95% CI): 2.84 (1.58, 5.12)). Conclusion. Being informed about blood transfusion and its life-saving benefits through either the education system or the experience made people more likely to intend to donate blood. Evidence-based interventions to retain blood donors as regular donors are recommended.