Introduction Epilepsy is a common neurological disorder associated with comorbidities and a reduced quality of life (QoL). Internalized stigma is negatively correlatedwiththe QoL, whereas high levels of resilience are associated with increased QoL. Although the stigma towards people with epilepsy (PWE) is expected to be higher in low-income settings than in high-income settings, further research is needed. This study aimed to examine the extent to which resilience and internalized stigma correlatewith the QoL in PWE from a low-income population. Material and Methods A cross-sectional, observational, descriptive study was conducted on 60 PWE who visited the Neurology Department of the Hospital de Clinicas (Buenos Aires, Argentina) between May and September 2022. Demographic and clinical data were collected. Participants completed the Quality of Life, Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), the Chronic Illness Anticipated Stigma Scale (CIASS), and the Resilience Scale (RS). Variables that showed a significant association with the QoL in the univariate analysis were included in a multiple regression model. Results Participants had a low overall QoL score, with a median of 59 (95 %CI: 57.2–61.8). They had an average level of education and a high rate of unemployment. Perceived stigma was higher in the workplace than in the medical or family settings. Univariate analysis revealed that the QoL was associated with internalized stigma score, resilience score, seizure frequency, seizure etiology, work status, and educational level. The multiple regressionrevealed a significant decrease in the QoL when perceived stigma increased (p = 0.0016) or when the cause of epilepsy was structural (p = 0,006) and a significant increase in the QoL when the resilience score was higher (p = 0.0004). Conclusion The QoL of PWE in a low-income context is strongly associated with their levels of resilience and internalized stigma. When addressing the social burden of epilepsy, resilience support should be increased in the care of PWE to reduce internalized stigma and improve the QoL.