diff --git a/packages/lib/models/Setting.test.ts b/packages/lib/models/Setting.test.ts
index a282e1936e..80d3e17ab4 100644
--- a/packages/lib/models/Setting.test.ts
+++ b/packages/lib/models/Setting.test.ts
@@ -330,6 +330,25 @@ describe('models/Setting', function() {
 		});
 	});
 
+	it('should not erase settings of parent profile', async () => {
+		// When a sub-profile settings are saved, we should ensure that the
+		// local settings of the root profiles are not lost.
+		// https://github.com/laurent22/joplin/issues/6459
+
+		await Setting.reset();
+
+		Setting.setValue('sync.target', 9); // Local setting (Root profile)
+		await Setting.saveAll();
+
+		await switchToSubProfileSettings();
+
+		Setting.setValue('sync.target', 2); // Local setting (Sub-profile)
+		await Setting.saveAll();
+
+		const globalSettings = JSON.parse(await readFile(`${Setting.value('rootProfileDir')}/settings-1.json`, 'utf8'));
+		expect(globalSettings['sync.target']).toBe(9);
+	});
+
 	it('all global settings should be saved to file', async () => {
 		for (const [k, v] of Object.entries(Setting.metadata())) {
 			if (v.isGlobal && v.storage !== SettingStorage.File) throw new Error(`Setting "${k}" is global but storage is not "file"`);
diff --git a/packages/lib/models/Setting.ts b/packages/lib/models/Setting.ts
index 012e4fa691..b5e320986e 100644
--- a/packages/lib/models/Setting.ts
+++ b/packages/lib/models/Setting.ts
@@ -305,7 +305,7 @@ class Setting extends BaseModel {
 		return BaseModel.TYPE_SETTING;
 	}
 
-	static async reset() {
+	public static async reset() {
 		if (this.saveTimeoutId_) shim.clearTimeout(this.saveTimeoutId_);
 		if (this.changeEventTimeoutId_) shim.clearTimeout(this.changeEventTimeoutId_);
 
@@ -316,6 +316,7 @@ class Setting extends BaseModel {
 		this.cache_ = [];
 		this.customMetadata_ = {};
 		this.fileHandler_ = null;
+		this.rootFileHandler_ = null;
 	}
 
 	public static get settingFilePath(): string {
@@ -2156,7 +2157,17 @@ class Setting extends BaseModel {
 		if (this.canUseFileStorage()) {
 			if (this.value('isSubProfile')) {
 				const { globalSettings, localSettings } = splitGlobalAndLocalSettings(valuesForFile);
-				await this.rootFileHandler.save(globalSettings);
+				const currentGlobalSettings = await this.rootFileHandler.load();
+
+				// When saving to the root setting file, we preserve the
+				// existing settings, which are specific to the root profile,
+				// and add the global settings.
+
+				await this.rootFileHandler.save({
+					...currentGlobalSettings,
+					...globalSettings,
+				});
+
 				await this.fileHandler.save(localSettings);
 			} else {
 				await this.fileHandler.save(valuesForFile);
diff --git a/packages/lib/testing/test-utils.ts b/packages/lib/testing/test-utils.ts
index 78dce7e0a1..2a23aa04ba 100644
--- a/packages/lib/testing/test-utils.ts
+++ b/packages/lib/testing/test-utils.ts
@@ -255,6 +255,10 @@ async function afterAllCleanUp() {
 	}
 }
 
+const settingFilename = (id: number): string => {
+	return `settings-${id}.json`;
+};
+
 async function switchClient(id: number, options: any = null) {
 	options = Object.assign({}, { keychainEnabled: false }, options);
 
@@ -271,18 +275,19 @@ async function switchClient(id: number, options: any = null) {
 	BaseItem.revisionService_ = revisionServices_[id];
 
 	await Setting.reset();
-	Setting.settingFilename = `settings-${id}.json`;
+	Setting.settingFilename = settingFilename(id);
 
 	Setting.setConstant('profileDir', rootProfileDir);
 	Setting.setConstant('rootProfileDir', rootProfileDir);
 	Setting.setConstant('resourceDirName', resourceDirName(id));
 	Setting.setConstant('resourceDir', resourceDir(id));
 	Setting.setConstant('pluginDir', pluginDir(id));
+	Setting.setConstant('isSubProfile', false);
 
 	await loadKeychainServiceAndSettings(options.keychainEnabled ? KeychainServiceDriver : KeychainServiceDriverDummy);
 
 	Setting.setValue('sync.target', syncTargetId());
-	Setting.setValue('sync.wipeOutFailSafe', false); // To keep things simple, always disable fail-safe unless explicitely set in the test itself
+	Setting.setValue('sync.wipeOutFailSafe', false); // To keep things simple, always disable fail-safe unless explicitly set in the test itself
 
 	// More generally, this function should clear all data, and so that should
 	// include settings.json
@@ -336,6 +341,7 @@ async function setupDatabase(id: number = null, options: any = null) {
 
 	Setting.setConstant('profileDir', rootProfileDir);
 	Setting.setConstant('rootProfileDir', rootProfileDir);
+	Setting.setConstant('isSubProfile', false);
 
 	if (databases_[id]) {
 		BaseModel.setDb(databases_[id]);