With worldwide prevalence rates between 10% and 20%, mental illness in children and adolescents is an issue for which culturally sensitive screening tools are needed. The Strengths & Difficulties Questionnaire (SDQ) is a commonly used measure that has been translated into numerous languages, although some research suggests issues with cross-cultural validity. Only four other studies have tested the Spanish-language SDQ in Latin America. In this study, we aimed to help fill this gap by assessing the factor structure of the parent or teacher version of the Spanish-language SDQ (for children ages 4–17) with 967 parent or other caregiver respondents of primary school-aged children (ages 4 to 17) in the Department of Intibucá, Honduras. When unable to find a good fitting factor model previously identified in the literature, we conducted split sample exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), along with measurement invariance testing with the best fitting EFA-extracted model based on gender for caregiver respondent and child gender. Results showed that while many EFA models had a good fit, CFI and TLI was < .90 for all extracted models when confirmed in the second sample with CFA. We then modified the best fitting extracted three-factor, 24-item model, which dropped item 15, by allowing select item residuals to correlate, increasing CFI and TLI to > .90 for female child gender. This modified three-factor model was partially invariant for configural and scalar models between child genders. Configural and scalar models would not converge for adult genders. Of note, metric models were not produced in Mplus related to items’ cross-loading on more than one factor. These findings suggest that the SDQ Spanish language parent or teacher version may not perform optimally cross-culturally in this area of Honduras. Future research should confirm these findings with other Honduran populations.