Health systems worldwide are moving toward use of information technology to improve healthcare delivery. However, this requires basic computer skills. This study assessed the computer literacy of nurses in Lesotho using a cross-sectional quantitative approach. A structured questionnaire with 32 standardized computer skills was distributed to 290 randomly selected nurses in Maseru District. Univariate and multivariate logistic regression analyses in Stata 13 were performed to identify factors associated with having inadequate computer skills. Overall, 177 (61%) nurses scored below 16 of the 32 skills assessed. Finding hyperlinks on Web pages (63%), use of advanced search parameters (60.2%), and downloading new software (60.1%) proved to be challenging to the highest proportions of nurses. Age, sex, year of obtaining latest qualification, computer experience, and work experience were significantly (P < .05) associated with inadequate computer skills in univariate analysis. However, in multivariate analyses, sex (P = .001), year of obtaining latest qualification (P = .011), and computer experience (P < .001) emerged as significant factors. The majority of nurses in Lesotho have inadequate computer skills, and this is significantly associated with having many years since obtaining their latest qualification, being female, and lack of exposure to computers. These factors should be considered during planning of training curriculum for nurses in Lesotho.