diff -u b/core/modules/responsive_image/src/ResponsiveImageStyleForm.php b/core/modules/responsive_image/src/ResponsiveImageStyleForm.php
--- b/core/modules/responsive_image/src/ResponsiveImageStyleForm.php
+++ b/core/modules/responsive_image/src/ResponsiveImageStyleForm.php
@@ -209,6 +209,20 @@
         // Remove the image style mappings since the breakpoint ID has changed.
         $form_state->unsetValue('keyed_styles');
       }
+
+      // Check that at least 1 image styles is selected when using sizes.
+      foreach ($form_state->getValue('keyed_styles') as $breakpoint_id => $multipliers) {
+        foreach ($multipliers as $multiplier => $image_style_mapping) {
+          if ($image_style_mapping['image_mapping_type'] === 'sizes') {
+            if (empty($image_style_mapping['sizes'])) {
+              $form_state->setError($form['keyed_styles'][$breakpoint_id][$multiplier]['sizes'], 'Sizes is required.');
+            }
+            if (empty(array_keys(array_filter($image_style_mapping['sizes_image_styles'])))) {
+              $form_state->setError($form['keyed_styles'][$breakpoint_id][$multiplier]['sizes_image_styles'], 'You have to select at least one image style.');
+            }
+          }
+        }
+      }
     }
   }