Introduction: Substance abuse is a major public health problem and its prevalence is increasing rapidly amongst university students in many African countries. Some studies on knowledge and substance use among students have been conducted in Nigeria, but few within Delta State. We assessed students’ knowledge of and attitude to substance abuse at a Nigerian University in Delta State.

Materials and Methods: A descriptive quantitative design was used. The department was randomly selected. Sample size was determined using Yamane’s formula for quantitative study: ny = N/(1+Ne2). A stratified sampling technique was used in selecting the participants at four levels of study (levels 100, 200, 300 and 400). The final subjects were randomly selected proportionally from the different strata. A total of 120 (64 males, 56 females) students constituted the sample size for this study. A questionnaire was used for data collection.

Result: Results showed that 92% of respondents had good knowledge of substance abuse. However, 24% exhibited negative attitude towards substance abuse. Inferential statistical analysis (Chi-square) showed no association between students’ knowledge of and attitude to substance abuse (χ² = 1.21, p > 0.05).

Conclusion: The students had good knowledge of substance abuse yet still engaged in substance abuse. Students frequently used substances like alcohol, cocaine, codeine, cigarette and tramadol. Effective counseling programme is recommended specifically in schools and families to help tackle this problem.