Aim: Children with epilepsy have an increased risk of difficulties with mathematics. Research into the mathematics difficulties of children with epilepsy, however, is limited. This study sought to determine whether the mathematics difficulties of children with epilepsy are related to mathematics anxiety over and above other previously identified factors (reading difficulties, generalized anxiety, and working memory).Method: Seventy-nine parents of children with epilepsy and 72 parents of typically developing children completed online questionnaires on their child's mathematics and reading difficulties (CLDQ; Colorado Learning Difficulties Questionnaire), mathematics anxiety (mAMAS; Modified Abbreviated Math Anxiety Scale), general anxiety (SCAS; Spence Child Anxiety Scale), and working memory (BRIEF-2; Brief Rating Inventory of Executive Function-2nd Edition). Questionnaires also collected demographic information and epilepsy variables.Results: Children with epilepsy had higher scores on the CLDQ mathematics subscale (CLDQm) and the mAMAS compared to typically developing children. Younger age of epilepsy onset, higher seizure fre-quency, and a greater number of anti-seizure medications accounted for 20.4% of the variance on the CLDQm. The CLDQ reading subscale (CLDQr) justified an additional 14% of the variance on the CLDQm. Finally, the mAMAS explained 20.2% of the variance on the CLDQm, after controlling for epilepsy variables and CLDQr. In contrast, the BRIEF-2 and SCAS did not account for a significant amount of variance on the CLDQm.Significance: Mathematics anxiety is the most significant contributor to mathematics difficulties experi-enced by children with epilepsy. Difficulties with reading and epilepsy factors also have significant, albeit smaller contributions to mathematics difficulties in this clinical population. Given the multiplicity of fac-tors contributing to mathematics difficulties, a comprehensive, multidisciplinary treatment is needed.& COPY; 2022 Published by Elsevier Inc.