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Background: Amyotrophic lateral sclerosis (ALS), often referred to as Lou Gehrig's disease, is a neurodegenerative disease of the upper and lower motor neurons, resulting in muscular atrophy and spasticity. It is a progressive, incurable illness with a mean survival from time of diagnosis of only 1-3 years. Aim of the Work: Therefore, this research aimed to study the QOL and functionality of sample of Egyptian patients with ALS during the pandemic of COVID-19. Patients and Methods: This cross-sectional study was conducted at Ain Shams University, in the period between August 1st, 2020, and March 30th, 2021. It included 74 patients recruited from neuromuscular unit Ain Shams University. Results: There was a statistically significant negative almost perfect correlation between total scores of ALSAQ-40 and ALSFR-R questionnaires. There was statistically significant negative almost perfect correlation between total scores of ALSAQ-40 and ALSFR-R questionnaires four domains i.e. bulbar, fine motor, gross motor, and respiratory. There was a statistically significant positive correlation between total scores of ALSAQ- 40 and age of the studied patients. There was no significant correlation between ALSAQ- 40 and time since disease onset. There was statistically significant association between total score of ALSAQ- 40 and gender of patients, where females had higher score than males. There was no statistically significant association between total score of ALSAQ-40 and special habits of patients. There was a statistically significant association between total score of ALSAQ-40 and presence of comorbidities (chronic illness, hypertension and diabetes) among the studied patients. Patients with chronic illness, hypertensives and diabetics had significantly higher scores (worse QoL). There was a statistically non-significant association between total score of ALSAQ-40 and disease type. There was a statistically significant association between total score of ALSAQ-40 and disease onset among the studied patients. Patients with bulbar onset had significantly higher scores (worse QoL). There was a statistically significant increase in total ALSAQ-40 scores after COVD-19 infection among the studied patients while there is statistically significant decrease in ALSFRS-R scores after catching COVID-19 infection. There was a non-significant correlation between time since onset and Quality of life as assessed by ALSAQ-40 and ALSFRS-R. Conclusion: The COVID-19 pandemic affected QoL of Egyptian patients with ALS. ALS patients were affected by restriction measures during COVID-19 pandemic. [ABSTRACT FROM AUTHOR]