The objective of this study was to explain loneliness as experienced by women with rheumatoid arthritis (RA) in a cross-cultural context. We studied 36 Egyptian female RA patients and 140 female Dutch RA patients.. Self-report data were collected about loneliness, physical and psychological health status, social support and social network, needs for help, attitudes and feelings of guilt. Loneliness was significantly higher among Egyptian (44.2 ± 32.3) than Dutch (12.9 ± 18.9) female RA patients (F = 54.3, p < 0.001). In Egypt, 36% of the variance of loneliness could be explained by worse affect (anxiety and depression; β = 0.51), fewer children (β = 0.31), and higher negative social support for the patients (β = 0.28) in multiple regression analysis. In the Netherlands, 35% of feeling lonely could be explained by worse affect scores (β = 0.52), less positive social support for the patients (β = 0.24), and a higher degree of disability (β = 0.21). Age of the patients and disease duration only explained 4% and 3% of the loneliness of RA patients in Egypt and the Netherlands, respectively. Female Egyptian RA patients experienced more loneliness than Dutch patients. Affect is the most important and constant variable in explaining loneliness in both countries. The role of the family in perceived loneliness is greater in Egypt than the Netherlands. Low social support received by patients is important in explaining loneliness in the Netherlands but not in Egypt.